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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.38, #1)

The fourth intracellular domain of G-protein coupling receptors: helicity, basicity and similarity to opsins by Michael S. Parker; Steven L. Parker (pp. 1-13).

The minimal size of the fourth intracellular domain of heptahelical G-protein coupling receptors (GPCRs) is close to 15 residues, and a juxtamembrane 15-residue segment is predicted as helical (Helix-8) in most of the receptors. Sequences of opsins, non-visual opsin-like (family A) GPCRs and Taste-2 receptors correspond with bovine rhodopsin at four positions in this tract. This is especially evident in monoamine receptors. In most GPCRs, the conserved juxtamembrane segment also has a large fraction of basic sidechains, and a considerable excess of cationic over anionic residues. The conservation is not dependent on the preferred G-protein α subunit or the overall length of the domain, indicating an additive speciation. In rod opsins and some A-GPCRs this segment has been shown to associate with the bilayer and to interact with G-proteins. The segment could also be involved in precoupling of receptors and transducers. These interactions could be helped by both the structural propensities and the high content of cationic sidechains.

Keywords: Basic sidechain abundance; Cytoplasmic helix; Juxtamembrane conservation; Receptor phylogeny; Transducer activation; Transducer recognition

Alimentary proteins, amino acids and cholesterolemia by François Blachier; Antonio H. Lancha Jr; Claire Boutry; Daniel Tomé (pp. 15-22).

Numerous data from both epidemiological and experimental origins indicate that some alimentary proteins and amino acids in supplements can modify the blood LDL cholesterol, HDL cholesterol and total cholesterol. After an initial approval of the health claim for soy protein consumption for the prevention of coronary heart disease, more recently it has been concluded from an overall analysis of literature that isolated soy protein with isoflavones only slightly decrease LDL and total cholesterol. Other plant extracts and also some proteins from animal origin have been reported to exert a lowering effect on blood cholesterol when compared with a reference protein (often casein). The underlying mechanisms are still little understood. Individual amino acids and mixture of amino acids have also been tested (mostly in animal studies) for their effects on cholesterol parameters and on cholesterol metabolism. Methionine, lysine, cystine, leucine, aspartate and glutamate have been tested individually and in combination in different models of either normo or hypercholesterolemic animals and found to be able to modify blood cholesterol and/or LDL cholesterol and/or HDL cholesterol. It is however not known if these results are relevant to human nutrition.

Keywords: Alimentary proteins; Amino acid supplementation; Cholesterol

Recent synthesis of aminophosphonic acids as potential biological importance by Emilia D. Naydenova; Petar T. Todorov; Kolio D. Troev (pp. 23-30).

Aminophosphonic acids are an important group of medicinal compounds, and their synthesis has been a focus of considerable attention in synthetic organic chemistry as well as medicinal chemistry. Although the phosphonic and carboxylic acid groups differ considerably with respect to shape, size, and acidity, α-aminophosphonic acids are considered to be structural analogues of the corresponding amino acids and the transition state mimics peptide hydrolysis. This review summarizes recent developments in the synthesis, characterization and biological activity of α-aminophosphonic acid and N-analogues. An account of both uses will be presented, emphasizing one of the potential future developments, and some implications in medicinal chemistry are also disclosed. In addition, a brief account on the characterization of N-(phosphonomethyl) glycine derivatives will be presented.

Keywords: α-Aminophosphonic acids; N-(phosphonomethyl) glycine; Phosphorus trichloride; Dimethyl-H-phosphonate; Biological activity

Exploring the therapeutic role of creatine supplementation by Bruno Gualano; Guilherme Giannini Artioli; Jacques R. Poortmans; Antonio Herbert Lancha Junior (pp. 31-44).

Creatine (Cr) plays a central role in energy provision through a reaction catalyzed by phosphorylcreatine kinase. Furthermore, this amine enhances both gene expression and satellite cell activation involved in hypertrophic response. Recent findings have indicated that Cr supplementation has a therapeutic role in several diseases characterized by atrophic conditions, weakness, and metabolic disturbances (i.e., in the muscle, bone, lung, and brain). Accordingly, there has been an evidence indicating that Cr supplementation is capable of attenuating the degenerative state in some muscle disorders (i.e., Duchenne and inflammatory myopathies), central nervous diseases (i.e., Parkinson’s, Huntington’s, and Alzheimer’s), and bone and metabolic disturbances (i.e., osteoporosis and type II diabetes). In light of this, Cr supplementation could be used as a therapeutic tool for the elderly. The aim of this review is to summarize the main studies conducted in this field and to highlight the scientific and clinical perspectives of this promising therapeutic supplement.

Keywords: Nutritional supplementation; Creatine; Therapeutic effects

Spectroscopic and structural elucidation of amino acid derivatives and small peptides: experimental and theoretical tools by Tsonko Kolev; Michael Spiteller; Bojidarka Koleva (pp. 45-50).

This mini review deals with the modern aspects of the spectroscopy and structural elucidation of amino acid derivatives and small biologically active compounds. Free peptide bond rotation in these systems yields various conformers, which possess differing biological activities. Another phenomenon is the intermolecular or intramolecular stacking observed in aromatic small peptides. Specifically, the main aim is to illustrate the successful application of the “complex tool”, consisting of a combination of the theoretical approximation methods with experimental linear polarized infrared (IR-LD) and/or Raman spectroscopy of oriented colloid suspensions in a nematic host. The possibilities and limitations of the approach for detailed vibrational assignment and structural elucidation of small peptides are discussed. Having in mind that physical and chemical properties of these systems can be precisely calculated by means of ab initio and DFT methods at Hartee-Fock, MP2 and B3LYP level of theory, varying basis sets, the results obtained allow a precise assignment of many vibrational bands to the corresponding normal modes, electronic structures and conformational state. The validity of the conclusions about the structure or vibrational properties of these systems have been supported, compared and/or additionally proved by the results from independent physical methods. In this respect ¹H and ¹³C-NMR, single crystal X-ray diffraction, HPLC tandem mass spectrometry as well as thermal methods are all employed. A well ordered crystal must first be grown in order to determine the molecular structure by the absolute method of single crystal X-ray diffraction. Although the 3D structures of peptides have been determined over the past decades, peptide crystallization is still a major obstacle to X-ray diffraction work, the presence of chiral centre/s makes for this difficulty. For this reason the “complex tool” presented can be regarded as an alternative method for obtaining of structural information in the solid-state. It is obviously that only absolute crystallographic method can yield geometric parameters, bond lengths and angles, but the spectroscopic method presented can provide information about the dihedral angles for cis- and trans-configurated amide groups, mutual disposition of the aromatic fragments in peptides. Its validity is illustrated by comparing the theoretical and spectroscopic results obtained with available crystallographic data. The mini review can serve as a useful source of information not only for specialists in IR spectroscopy but, also, for other scientists, working in the field of structural analysis of amino acid derivatives and other small biologically active systems.

A novel key–lock mechanism for inactivating amino acid neurotransmitters during transit across extracellular space by Morris H. Baslow (pp. 51-55).

There are two kinds of neurotransmissions that occur in brain. One is neuron to neuron at synapses, and the other is neuron to glia via extracellular fluid (ECF), both of which are important for maintenance of proper neuronal functioning. For neuron to neuron communications, several potent amino acid neurotransmitters are used within the confines of synaptic space. However, their presence at elevated concentrations in extra-synaptic space could be detrimental to well organized neuronal functioning. The significance of the synthesis and release of N-acetylaspartylglutamate (NAAG) by neurons has long been a puzzle since glutamate (Glu) itself is the “key” that can interact with all Glu receptors on membranes of all cells. Nonetheless, neurons synthesize this acetylated dipeptide, which cannot be catabolized by neurons, and release it to ECF where its specific physiological target is the Glu metabotropic receptor 3 on the surface of astrocytes. Since Glu is excitotoxic at elevated concentrations, it is proposed that formation and release of NAAG by neurons allows large quantities of Glu to be transported in ECF without the risk of injurious excitotoxic effects. The metabolic mechanism used by neurons is a key–lock system to detoxify Glu during its intercellular transit. This is accomplished by first synthesizing N-acetylaspartate (NAA), and then joining this molecule via a peptide bond to Glu. In this paper, a hypothesis is presented that neurons synthesize a variety of relatively nontoxic peptides and peptide derivatives, including NAA, NAAG, homocarnosine (γ-aminobutyrylhistidine) and carnosine (β-alanylhistidine) from potent excitatory and inhibitory amino acids for the purpose of releasing them to ECF to function as cell-specific neuron-to-glia neurotransmitters.

Keywords: Brain; N-acetylaspartate; N-acetylaspartylglutamate; Carnosine; Homocarnosine; Glutamate; Metabotropic glutamate receptor 3

Intracerebroventricular injection of L-proline and D-proline induces sedative and hypnotic effects by different mechanisms under an acute stressful condition in chicks by K. Hamasu; K. Shigemi; Y. Tsuneyoshi; H. Yamane; H. Sato; D. M. Denbow; M. Furuse (pp. 57-64).

The central effects of L-proline, D-proline and trans-4-hydroxy-L-proline were investigated by using the acute stressful model with neonatal chicks in Experiment 1. Sedative and hypnotic effects were induced by all compounds, while plasma corticosterone release under isolation stress was only attenuated by L-proline. To clarify the mechanism by which L-proline and D-proline induce sedative and hypnotic effects, the contribution of the strychnine-sensitive glycine receptor (glycine receptor) and N-methyl-D-aspartate glutamate receptor (NMDA receptor) were further investigated. In Experiments 2–3, the glycine receptor antagonist strychnine was co-injected intracerebroventricular (i.c.v.) with L-proline or D-proline. The suppression of isolation-induced stress behavior by D-proline was attenuated by strychnine. However, the suppression of stress behavior by L-proline was not attenuated. In Experiment 4, the NMDA receptor antagonist (+)-MK-801 was co-injected i.c.v. with L-proline. The suppression of stress behavior by L-proline was attenuated by (+)-MK-801. These results indicate that L-proline and D-proline differentially induce sedative and hypnotic effects through NMDA and glycine receptors, respectively.

Keywords: CNS; Stress; Strychnine; (+)-MK-801; Strychnine-sensitive glycine receptor; NMDA receptor

Metabonomics and population studies: age-related amino acids excretion and inferring networks through the study of urine samples in two Italian isolated populations by Pio D’Adamo; Sheila Ulivi; Amerigo Beneduci; Gabriele Pontoni; Giovambattista Capasso; Carmela Lanzara; Gilberto Andrighetto; Uros Hladnik; Virginia Nunes; Manuel Palacin; Paolo Gasparini (pp. 65-73).

The study of two different Italian isolated populations was combined with a metabonomic approach to better understand tubular handling of amino acids. Levels of amino acids and metabolites have been analyzed by Nucleic Magnetic Resonance and expressed as ratio vs urinary creatinine concentration (mmol/mol). For most of the amino acids there is an age-related U shape pattern of excretion, with the peaks during childhood and old age, and a significant reduction in the adult age. Hierarchical cluster analysis has clearly identified three groups clustering the same amino acids: His, Thr and Ala (group one); Gly and Phe (group two) and a third larger one. Results have been further confirmed by factor and regression analysis, and used to confirm and, in some cases, infer new amino acids networks. As a matter of facts, the identification of strong evidences for clustering of urine excretion of several neutral amino acids suggests the predominant impact of relevant and common transporters

Keywords: Amino acids; Tubular handling; Metabonomics; Population studies

The β1-adrenergic receptor mediates extracellular signal-regulated kinase activation via Gαs by Junfang Zheng; Hui Shen; Ying Xiong; Xiaomei Yang; Junqi He (pp. 75-84).

β-Adrenergic receptors can activate extracellular signal-regulated kinases (ERKs) via different mechanisms. In this study, we investigated the molecular mechanism of β1-adrenergic receptor (β1AR)-mediated ERK activation in African green monkey kidney COS-7 cells. Treatment of cells with isoproterenol (ISO), a β1AR selective agonist, induced phosphorylation of ERK1/2 in a dose-dependent manner. ISO-stimulated ERK phosphorylation was not influenced by the Gβγ inhibitor, βAR kinase carboxyl terminal (βARKct) or by the Gi inhibitor, pertussis toxin (PTX), but it was clearly abolished via inhibition of protein kinase A (PKA) with H89, or of mitogen-activated protein kinase kinase (MEK1) with PD98059, revealing that the Gαs subunit is involved in ERK regulation through the PKA/MEK1 pathway. We also tested the effect of the adenylate cyclase activator forskolin on ERK activation, and the result was identical to that of ISO stimulation. Moreover, pretreatment with the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor AG1478 or with the Src tyrosine kinase inhibitor PP2 did not affect ERK activation. These observations suggest a mechanism of β1AR-mediated ERK activity that involves the Gαs subunit, but not EGFR or Src tyrosine kinase.

Keywords: Src-related kinase; G protein; Protein kinase A; Epidermal growth factor receptor; Mitogen-activated protein kinase

Camphoric acid stimulates osteoblast differentiation and induces glutamate receptor expression by Su-Ui Lee; Nam Sook Kang; Yong Ki Min; Seong Hwan Kim (pp. 85-93).

We found that camphoric acid significantly stimulated the differentiation of mouse osteoblastic MC3T3-E1 subclone 4 cells, as indicated by the induction of markers of osteoblastic differentiation. To elucidate the mechanism of action of camphoric acid in osteoblast differentiation, we evaluated the induction of transient receptor potential (TRP) cation channel family members and glutamate signaling molecules. TRPM7 and TRPV1 were highly expressed, but their expression was unaffected by camphoric acid. Camphoric acid is structurally similar to glutamate receptor ligands and significantly induced the expression of NMDAR1, GluR3/4, and mGluR8. However, camphoric acid exhibited weak regulatory activity toward glutamate receptors in a radioligand binding assay. Camphoric acid also significantly induced the activation of NF-κB and AP-1. Together, these data suggest that the stimulatory effect of camphoric acid on osteoblast differentiation was the result of its ability to induce mRNA expression of glutamate signaling molecules and to activate transcription factors.

Keywords: Camphoric acid; Osteoblastic cells; Differentiation; Glutamate receptors; Transcription factors

Dietary arginine supplementation enhances antioxidative capacity and improves meat quality of finishing pigs by Xianyong Ma; Yingcai Lin; Zongyong Jiang; Chuntian Zheng; Guilian Zhou; Deqian Yu; Ting Cao; Jun Wang; Fang Chen (pp. 95-102).

The present study was conducted to test the hypothesis that dietary arginine supplementation may improve meat quality of finishing pigs. Beginning at ~60 kg body weight, pigs were fed a corn- and soybean meal-based diet supplemented with 0, 0.5 or 1% l-arginine until they reached a body weight of ~110 kg. On the last day of the experiment, pigs were food-deprived for 16 h before blood samples were obtained for analysis of amino acids, insulin, and other metabolites. Immediately thereafter, pigs were slaughtered for determination of carcass composition, muscle biochemical parameters, and meat quality. The result showed that arginine did not affect pig growth performance or carcass traits. However, 1% arginine decreased drip loss of pork muscle at 48 h postmortem, while increasing intramuscular fat content (P < 0.05). Supplementing 0.5 or 1% arginine to the diet increased arginine concentration and decreased cortisol level in serum, while enhancing antioxidative capacity and glutathione peroxidase activity in serum (P < 0.05). Additionally, 1% arginine increased antioxidative capacity in skeletal muscle (P < 0.05). Furthermore, 0.5 or 1% arginine decreased the cortisol receptor mRNA level in muscle (P < 0.05). Collectively, these results indicate that supplemental arginine improved meat quality and attenuated oxidative stress of finishing pigs.

Keywords: Arginine; Finishing pig; Meat quality; Antioxidant capacity; Stress

Synthesis, characterization and hybridization studies of an alternate nucleo-ε/γ-peptide: complexes formation with natural nucleic acids by G. N. Roviello; D. Musumeci; C. Pedone; E. M. Bucci (pp. 103-111).

In order to develop new oligodeoxyribonucleotide (ODN) analogs to be used in biotechnological applications, we report here the synthesis, characterization and nucleic acid binding studies of novel nucleopeptides, that we called ε-lys/γ-dabPNAs, containing a backbone of alternated l-diaminobutyric acid and l-lysine moieties. Exploring the hybridization properties of the new ODN analog, we found, by circular dichroism and UV spectroscopies, that a homothymine ε-lys/γ-dabPNA hexamer binds both DNA and RNA of complementary sequence. Furthermore, human serum stability assays on the alternate nucleopeptide evidenced a noteworthy degradation resistance. These results encourage us to deepen the knowledge of this analog, in order to evaluate its possible use in antigene/antisense or diagnostic applications.

Keywords: Nucleopeptides; ODN analogs; ε-lys/γ-dabPNAs; Binding studies; Serum stability

Potential enzyme toxicity of perfluorooctanoic acid by Ling-Ling Wu; Ling Chen; Chao Song; Xi-Wei Liu; Hui-Ping Deng; Nai-Yun Gao; Hong-Wen Gao (pp. 113-120).

Using equilibrium dialysis, isothermal titration calorimetry (ITC) and circular dichroism (CD), the interactions of perfluorooctanoic acid (PFOA) and lysozyme were investigated under normal human physiological conditions, i.e., at pH 4.40, 6.00 and 7.40 at 37°C in 0.15 M electrolyte. A simple and rapid spectrophotometric method was developed for determining PFOA concentrations. Interactions between PFOA and lysozyme were found to result from non-specific non-covalent bonds—F/N and F/O affinity, ion-pair attraction, hydrogen bond, hydrophobic interaction and van der Waals force—and were affected by chemical adsorption to monolayers. The results indicated that binding of PFOA altered the secondary structure and activity of lysozyme. This work provides a useful experimental strategy for research into the enzyme toxicity of organic chemicals, e.g., food additives and organic contaminants, and it may help to elucidate the molecular toxicology of human health risks.

Keywords: Lysozyme; Perfluorooctanoic acid; Non-covalent binding; Enzyme toxicity; Structural change

Effect of helix-promoting strategies on the biological activity of novel analogues of the B-chain of INSL3 by Fazel Shabanpoor; Richard A. Hughes; Suode Zhang; Ross A. D. Bathgate; Sharon Layfield; Mohammed Akhter Hossain; Geoffrey W. Tregear; Frances Separovic; John D. Wade (pp. 121-131).

Insulin-like 3 (INSL3) is a novel circulating peptide hormone that is produced by testicular Leydig cells and ovarian thecal and luteal cells. In males, INSL3 is responsible for testicular descent during foetal life and suppresses germ cell apoptosis in adult males, whereas in females, it causes oocyte maturation. Antagonists of INSL3 thus have significant potential clinical application as contraceptives in both males and females. Previous work has shown that the INSL3 receptor binding region is largely confined to the B-chain central α-helix of the hormone and a conformationally constrained analogue of this has modest receptor binding and INSL3 antagonist activity. In the present study, we have employed and evaluated several approaches for increasing the α-helicity of this peptide in order to better present the key receptor binding residues and increase its affinity for the receptor. Analogues of INSL3 with higher α-helicity generally had higher receptor binding affinity although other structural considerations limit their effectiveness.

Keywords: INSL3; RXFP2; Lactam-constraint; Disulfide-constraint; Helicity; Peptide

A preparation of N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids by Maria Luisa Di Gioia; Antonella Leggio; Angelo Liguori; Francesca Perri; Carlo Siciliano; Maria Caterina Viscomi (pp. 133-143).

A convenient route for the synthesis of lipophilic N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids, interesting building blocks to be used for the preparation of N-methylated peptides, is presented. Both nosyl- and Fmoc-protected monomers are accessible, so these compounds can be used in solution as well as in solid phase peptide synthesis. The methodology is based on the use of benzhydryl group to protect temporarily the carboxyl function of N-nosyl-α-amino acids and on the subsequent methylation of the N-nosyl-α-amino acid benzhydryl esters with diazomethane. The benzhydryl esters offer several beneficial features such as simple preparation, stability to methylation and selective deprotection under mild conditions. The overall procedure is highly efficient in that the adopted conditions keep the chiral integrity of amino acid precursors and the process does not require chromatographic purification of the methylated products.

Keywords: N-Fmoc-N-methyl-α-amino acid; N-Methyl-N-nosyl-α-amino acid; Benzhydryl esters; Diazomethane; Diphenyldiazomethane; N-Methylated dipeptides

Leucine affects the fibroblastic Vero cells stimulating the cell proliferation and modulating the proteolysis process by Estela Maria Gonçalves; Maria Cristina Cintra Gomes-Marcondes (pp. 145-153).

Branched-chain amino acids, especially leucine, exert regulatory influences on protein and carbohydrate metabolism, ribosome biogenesis and gene expression. This study investigated the effects of leucine in fibroblastic cells analysing viability, proliferation, morphology, proteolysis enzymes activities and protein turnover. After exposure to culture medium enriched with 25 or 50 μM leucine for 24, 48 and 72 h, Vero cells have no alterations on viability and morphology. Leucine-treated cells showed increase on alkaline phosphatase activity and proliferation. The protein synthesis was slightly increased, whereas the protein degradation showed a deep reduction after leucine incubation. The chymotrypsin-like, cathepsin B and H and calpain activities were decreased in leucine-treated cells. In conclusion, the proteolytic pathways and the total protein degradation were modulated by leucine in Vero cells. Our observations support the concept that Vero cells may represent a new model for protein turnover study.

Keywords: Leucine; Protein metabolism; Cell proliferation; Vero cells

Papaya latex enzymes capable of detoxification of gliadin by H. J. Cornell; W. Doherty; T. Stelmasiak (pp. 155-165).

Assay of fractions obtained from ion exchange chromatography of papaya latex on CM Sephadex-C50, size exclusion chromatography on Sephacryl S-300 and size exclusion HPLC have provided an insight into the relative contributions of the gluten-detoxifying enzymes present. This outcome has been achieved by the use of the above chromatographic techniques, coupled with assays of lysosomal activity, protease activity using benzylarginine ethyl ester (BAEE) as substrate, prolyl endopeptidase (PEP) using glycylprolylnitroanilide and a prolidase assay using acetylprolylglycine. These procedures have shown that the activity in papaya latex is due largely to caricain and to a lesser extent, chymopapain and glutamine cyclotransferase. The presence of caricain and these other enzymes was confirmed by mass spectrometry of trypsin digests of the most active fraction obtained by CM Sephadex-C50 chromatography and size exclusion HPLC. Fractions rich in caricain would be suitable for enzyme therapy in gluten intolerance and appear to have synergistic action with porcine intestinal extracts.

Keywords: Gluten intolerance; Enzyme therapy; Gliadins; Papaya; Caricain

Effects of α-ketoglutarate on neutrophil intracellular amino and α-keto acid profiles and ROS production by Jörg Mühling; F. Tussing; K. A. Nickolaus; R. Matejec; M. Henrich; H. Harbach; M. Wolff; K. Weismüller; J. Engel; I. D. Welters; T. W. Langefeld; M. Fuchs; M. A. Weigand; M. C. Heidt (pp. 167-177).

The aim of this study was to determine the effects of α-ketoglutarate on neutrophil (PMN), free α-keto and amino-acid profiles as well as important reactive oxygen species (ROS) produced [superoxide anion (O₂ ⁻), hydrogen peroxide (H₂O₂)] and released myeloperoxidase (MPO) acitivity. Exogenous α-ketoglutarate significantly increased PMN α-ketoglutarate, pyruvate, asparagine, glutamine, asparatate, glutamate, arginine, citrulline, alanine, glycine and serine in a dose as well as duration of exposure dependent manner. Additionally, in parallel with intracellular α-ketoglutarate changes, increases in O₂ ^– formation, H₂O₂-generation and MPO acitivity have also been observed. We therefore believe that α-ketoglutarate is important for affecting PMN “susceptible free amino- and α-keto acid pools” although important mechanisms and backgrounds are not yet completely explored. Moreover, our results also show very clearly that changes in intragranulocytic α-ketoglutarate levels are relevant metabolic determinants in PMN nutrition considerably influencing and modulating the magnitude and quality of the granulocytic host defense capability as well as production of ROS.

Keywords: α-Ketoglutarate; Neutrophil; Amino acids; α-Keto acids; Immune function

Determining important regulatory relations of amino acids from dynamic network analysis of plasma amino acids by Nahoko Shikata; Yukihiro Maki; Masahiko Nakatsui; Masato Mori; Yasushi Noguchi; Shintaro Yoshida; Michio Takahashi; Nobuo Kondo; Masahiro Okamoto (pp. 179-187).

The changes in the concentrations of plasma amino acids do not always follow the flow-based metabolic pathway network. We have previously shown that there is a control-based network structure among plasma amino acids besides the metabolic pathway map. Based on this network structure, in this study, we performed dynamic analysis using time-course data of the plasma samples of rats fed single essential amino acid deficient diet. Using S-system model (conceptual mathematical model represented by power-law formalism), we inferred the dynamic network structure which reproduces the actual time-courses within the error allowance of 13.17%. By performing sensitivity analysis, three of the most dominant relations in this network were selected; the control paths from leucine to valine, from methionine to threonine, and from leucine to isoleucine. This result is in good agreement with the biological knowledge regarding branched-chain amino acids, and suggests the biological importance of the effect from methionine to threonine.

Keywords: Plasma amino acids; Relation; Regulation; Network; Amino acid deficiency; Dynamic

Diazepam administration after prolonged status epilepticus reduces neurodegeneration in the amygdala but not in the hippocampus during epileptogenesis by Felicia Qashu; Taiza H. Figueiredo; Vassiliki Aroniadou-Anderjaska; James P. Apland; Maria F. M. Braga (pp. 189-197).

An episode of status epilepticus (SE), if left untreated, can lead to death, or brain damage with long-term neurological consequences, including the development of epilepsy. The most common first-line treatment of SE is administration of benzodiazepines (BZs). However, the efficacy of BZs in terminating seizures is reduced with time after the onset of SE; this is accompanied by a reduced efficacy in protecting the hippocampus against neuronal damage, and is associated with impaired function and internalization of hippocampal GABA_A receptors. In the present study, using Fluoro-Jade C staining, we found that administration of diazepam to rats at 3 h after the onset of kainic acid-induced SE, at a dose sufficient to terminate SE, had no protective effect on the hippocampus, but produced a significant reduction in neuronal degeneration in the amygdala, piriform cortex, and endopiriform nucleus, examined on days 7–9 after SE. Thus, in contrast to the hippocampus, the amygdala and other limbic structures are responsive to neuroprotection by BZs after prolonged SE, suggesting that GABA_A receptors are not significantly altered in these structures during SE.

Keywords: Amygdala; Hippocampus; Benzodiazepines; Status epilepticus; Neurodegeneration; Epileptogenesis

Gaussian process: an alternative approach for QSAM modeling of peptides by Peng Zhou; Xiang Chen; Yuqian Wu; Zhicai Shang (pp. 199-212).

Different statistical modeling methods (SMMs) are used for nonlinear system classification and regression. On the basis of Bayesian probabilistic inference, Gaussian process (GP) is preliminarily used in the field of quantitative structure-activity relationship (QSAR) but has not yet been applied to quantitative sequence-activity model (QSAM) of biosystems. This paper proposes the application of GP as an alternative tool for the QSAM modeling of peptides. To investigate the modeling performance of GP, three classical peptide panels were used: Angiotensin-I converting enzyme inhibitory dipeptides, bradykinin-potentiating pentapeptides and cationic antimicrobial pentadecapeptides. On this basis, we made a comprehensive comparison between the GP and some widely used SMMs such as PLS, artificial neural network (ANN) and support vector machine (SVM), and gave the conclusions as follow: (1) for those of structurally complicated peptides, particularly the polypeptides, linear PLS was incapable of capturing all dependences hidden in the peptide systems, (2) even in assistance with the monitoring technique, ANN was inclined to be overtrained in the cases of insufficient number of peptide samples, (3) SVM and GP performed best for the three peptide panels. Moreover, since GP was able to correlate the linear and nonlinear-hybrid relationship, it was slightly superior to SVM at most peptide sets.

Keywords: Gaussian process; Statistical modeling method; Quantitative sequence-activity model; Peptide; Amino acid descriptor

Antifreeze glycopeptide analogues: microwave-enhanced synthesis and functional studies by Carolin Heggemann; Carsten Budke; Benjamin Schomburg; Zsuzsa Majer; Marco Wißbrock; Thomas Koop; Norbert Sewald (pp. 213-222).

Antifreeze glycoproteins enable life at temperatures below the freezing point of physiological solutions. They usually consist of the repetitive tripeptide unit (-Ala-Ala-Thr-) with the disaccharide α-d-galactosyl-(1–3)-β-N-acetyl-d-galactosamine attached to each hydroxyl group of threonine. Monoglycosylated analogues have been synthesized from the corresponding monoglycosylated threonine building block by microwave-assisted solid phase peptide synthesis. This method allows the preparation of analogues containing sequence variations which are not accessible by other synthetic methods. As antifreeze glycoproteins consist of numerous isoforms they are difficult to obtain in pure form from natural sources. The synthetic peptides have been structurally analyzed by CD and NMR spectroscopy in proton exchange experiments revealing a structure as flexible as reported for the native peptides. Microphysical recrystallization tests show an ice structuring influence and ice growth inhibition depending on the concentration, chain length and sequence of the peptides.

Keywords: Bioorganic chemistry; Microwave synthesis; Glycopeptides; Recrystallization; Circular dichroism

mTOR phosphorylated at S2448 binds to raptor and rictor by M. Rosner; N. Siegel; A. Valli; C. Fuchs; M. Hengstschläger (pp. 223-228).

In mammalian cells, the mammalian target of rapamycin (mTOR) forms an enzyme complex with raptor (together with other proteins) named mTOR complex 1 (mTORC1), of which a major target is the p70 ribosomal protein S6 kinase (p70S6K). A second enzyme complex, mTOR complex 2 (mTORC2), contains mTOR and rictor and regulates the Akt kinase. Both mTORC1 and mTORC2 are regulated by phosphorylation, complex formation and localization. So far, the role of p70S6K-mediated mTOR S2448 phosphorylation has not been investigated in detail. Here, we report that endogenous mTOR phosphorylated at S2448 binds to both, raptor and rictor. Experiments with chemical inhibitors of the mTOR kinase and of the phosphatidylinositol-3-kinase revealed that downregulation of mTOR S2448 phosphorylation correlates with decreased mTORC1 activity but can occur decoupled of effects on mTORC2 activity. In addition, we found that the correlation of the mTOR S2448 phosphorylation status with mTORC1 activity is not a consequence of effects on the assembly of mTOR protein and raptor. Our data allow new insights into the role of mTOR phosphorylation for the regulation of its kinase activity.

Keywords: mTOR; Phosphorylation; Raptor; Rictor

d-Aspartate binding sites in rat Harderian gland by Marcello Di Giovanni; Enza Topo; Alessandra Santillo; Antimo D’Aniello; Gabriella Chieffi Baccari (pp. 229-235).

Radioligand binding of d-[³H]aspartic and l-[³H]glutamic acids to plasma membranes from rat Harderian gland was evaluated. Binding was optimal under physiological conditions of pH and temperature, and equilibrium was reached within 50 min. Specific binding for d-Asp and l-Glu was saturable, and Eadie–Hofstee analysis revealed interaction with a single population of binding sites (for d-Asp K _d = 860 ± 28 nM, B _max = 27.2 ± 0.5 pmol/mg protein; for l-Glu, K _d = 580 ± 15 nM and B _max = 51.3 ± 0.8 pmol/mg protein). l-[³H]glutamate had higher affinity and a greater percentage of specific binding than did d-[³H]aspartate. The pharmacological binding specificity of l-[³H]glutamate indicated an interaction with NMDA-type receptors. Specifically, the order of potency of the displacing compound tested was l-Glu > d-Asp > NMDA > MK801 > d-AP5 > glycine. For d-[³H]aspartate, the data revealed an interaction of d-Asp with either NMDA-type receptors or putative specific binding sites.

Keywords: Harderian gland; d-Aspartate; Binding sites; Rat

Protective effects of taurine against endotoxin-induced acute liver injury after hepatic ischemia reperfusion by Feng Zhang; Yahong Mao; Haiquan Qiao; Hongchi Jiang; Haifeng Zhao; Xiaoning Chen; Liquan Tong; Xueying Sun (pp. 237-245).

Hepatic ischemia reperfusion (HIR) not only results in liver injury, but also leads to endotoxemia, which aggravates HIR-induced liver injury and dysfunction, or even causes liver failure. Taurine has been shown to protect organs from ischemia reperfusion or endotoxin by its anti-oxidant and anti-inflammatory activities. The aim of this study was to investigate whether taurine could attenuate endotoxin-induced acute liver injury after HIR. Wistar rats subjected to 30 min of hepatic ischemia followed by reperfusion and lipopolysaccharide (LPS) (0.5 mg/kg) administration, exhibited liver dysfunction (elevated serum levels of ALT, AST and LDH) and hepatic histopathological alteration. The serum levels of TNF-α and production of myeloperoxidase (MPO) and malondialdehyde (MDA) in liver tissues and apoptosis of hepatocytes were also increased after the combination of HIR and LPS. However, pre-administration of taurine protected livers from injury induced by the combination of HIR + LPS as the histological score, apoptotic index, MPO activity and production of MDA in liver tissues, and serum levels of AST, ALT, LDH and TNF-α, were significantly reduced. The expression of caspase-3, Fas and Fas ligand was upregulated in homogenates of livers from rats subjected to HIR and LPS, and this elevated expression could be inhibited by taurine. In summary, the results further emphasize the potential utilization of taurine in protecting livers against endotoxin-induced injury especially after HIR, by its anti-inflammatory, anti-oxidative and anti-apoptotic activities.

Keywords: Ischemia reperfusion; Endotoxemia; Taurine; Liver; Myeloperoxidase; Inflammatory cytokine; Apoptosis

d-Amino acid dehydrogenase from Helicobacter pylori NCTC 11637 by Minoru Tanigawa; Tomomitsu Shinohara; Makoto Saito; Katsushi Nishimura; Yuichiro Hasegawa; Sadao Wakabayashi; Morio Ishizuka; Yoko Nagata (pp. 247-255).

Helicobacter pylori is a microaerophilic bacterium, associated with gastric inflammation and peptic ulcers. d-Amino acid dehydrogenase is a flavoenzyme that digests free neutral d-amino acids yielding corresponding 2-oxo acids and hydrogen. We sequenced the H. pylori NCTC 11637 d-amino acid dehydrogenase gene, dadA. The primary structure deduced from the gene showed low similarity with other bacterial d-amino acid dehydrogenases. We purified the enzyme to homogeneity from recombinant Escherichia coli cells by cloning dadA. The recombinant protein, DadA, with 44 kDa molecular mass, possessed FAD as cofactor, and showed the highest activity to d-proline. The enzyme mediated electron transport from d-proline to coenzyme Q₁, thus distinguishing it from d-amino acid oxidase. The apparent K _m and V _max values were 40.2 mM and 25.0 μmol min⁻¹ mg⁻¹, respectively, for dehydrogenation of d-proline, and were 8.2 μM and 12.3 μmol min⁻¹ mg⁻¹, respectively, for reduction of Q₁. The respective pH and temperature optima were 8.0 and 37°C. Enzyme activity was inhibited markedly by benzoate, and moderately by SH reagents. DadA showed more similarity with mammalian d-amino acid oxidase than other bacterial d-amino acid dehydrogenases in some enzymatic characteristics. Electron transport from d-proline to a c-type cytochrome was suggested spectrophotometrically.

Keywords: d-Amino acid dehydrogenase; d-Proline; Gene cloning; Helicobacter pylori ; Bacterial respiration

Transglutaminase-dependent antiproliferative and differentiative properties of nimesulide on B16-F10 mouse melanoma cells by Angelo Gismondi; Alessandro Lentini; Claudio Tabolacci; Bruno Provenzano; Simone Beninati (pp. 257-262).

The aim of this study was to collect evidences on the role of transglutaminase (TG, E.C.2.3.2.13) in the antineoplastic properties exerted by nimesulide (NMS), a non-steroidal anti-inflammatory drug, on murine B16-F10 melanoma cells. Treatment of melanoma cells with nimesulide produces a considerable reduction of cell proliferation, paralleled by a remarkable decrease of the intracellular concentration of polyamines spermidine and spermine. NMS treatment induces cancer cell differentiation, likely through the observed enhancement of TG and tyrosinase activities and increase of melanin production, well known markers of melanocyte differentiation. The overall results highlight the possibility that nimesulide acts as antineoplastic agent likely through the induction of intracellular TG activity.

Keywords: Nimesulide; Polyamines; Transglutaminase; Differentiation; Tyrosinase; Melanin

Identifying protein–protein interaction sites in transient complexes with temperature factor, sequence profile and accessible surface area by Rong Liu; Wenchao Jiang; Yanhong Zhou (pp. 263-270).

Transient protein–protein interactions play a vital role in many biological processes, such as cell regulation and signal transduction. A nonredundant dataset of 130 protein chains extracted from transient complexes was used to analyze the features of transient interfaces. It was found that besides the two well-known features, sequence profile and accessible surface area (ASA), the temperature factor (B-factor) can also reflect the differences between interface and the rest of protein surface. These features were utilized to construct support vector machine (SVM) classifiers to identify interaction sites. The results of threefold cross-validation on the nonredundant dataset show that when B-factor was used as an additional feature, the prediction performance can be improved significantly. The sensitivity, specificity and correlation coefficient were raised from 54 to 62%, 41 to 45% and 0.20 to 0.29, respectively. To further illustrate the effectiveness of our method, the classifiers were tested with an independent set of 53 nonhomologous protein chains derived from benchmark 2.0. The sensitivity, specificity and correlation coefficient of the classifier based on the three features were 63%, 45% and 0.33, respectively. It is indicated that our classifiers are robust and can be applied to complement experimental techniques in studying transient protein–protein interactions.

Keywords: Protein–protein interactions; Transient interface; Sequence profile; Temperature factor; Accessible surface area; Support vector machine

Prevention of hypercholesterolemia and atherosclerosis in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail by taurine supplementation by Shigeru Murakami; T. Sakurai; H. Tomoike; M. Sakono; T. Nasu; N. Fukuda (pp. 271-278).

The effects of taurine supplementation on the serum cholesterol levels and the progression of atherosclerosis were investigated in the hyperlipidemia- and atherosclerosis-prone Japanese (LAP) quail. The ingestion of a high-cholesterol diet containing 1% cholesterol by LAP quails for 60 days resulted in a marked elevation in serum non-HDL cholesterol and triglyceride, as well as severe aortic lesions with lipid droplets. An immunohistochemical study showed that the lesion consisted of mainly lipid-rich macrophages and T cells. Sixty-day taurine supplementation (1% in drinking tap water) to LAP quails fed high-cholesterol diet containing 1% cholesterol significantly reduced serum non-HDL cholesterol from 4,549 to 2,350 mg/dl. The serum triglyceride level also decreased after taurine supplementation from 703 to 392 mg/dl. Although the HDL cholesterol level significantly decreased due to the high-cholesterol diet, it recovered to the control level fed a regular diet in response to taurine. Bile acid production was stimulated and hepatic cholesterol was reduced by taurine supplementation. A quantitative analysis using aortic cross-sections showed that areas of oil-red O positive lipid accumulation significantly decreased by 74% after taurine supplementation. These results demonstrated the lipid-lowering and anti-atherosclerotic effects of taurine in a diet-induced hyperlipidemic LAP quail model. The prevention of atherosclerosis by taurine is mainly attributed to an improvement in the serum cholesterol and triglyceride levels, which may be related to changes in the hepatic cholesterol metabolism.

Keywords: Taurine; LAP quail; Atherosclerosis; Hypercholesterolemia

Synthesis of orthogonally protected azahistidine: application to the synthesis of a GHK analogue by Stéphane Roux; Melinda Ligeti; David-Alexandre Buisson; Bernard Rousseau; Jean-Christophe Cintrat (pp. 279-286).

The synthesis of various orthogonally protected azahistidine derivatives are obtained via 1,3-dipolar cycloaddition reactions. The newly obtained amino-acids can be selectively deprotected either at the side chain or at the N-terminus of the amino acid and should thus allow the use of these derivatives in (solid phase) peptide synthesis.

Keywords: Click chemistry; Huisgen cycloaddition; Triazole; Azahistidine; GHK

Catalytic effects of histidine enantiomers and glycine on the formation of dileucine and dimethionine in the salt-induced peptide formation reaction by Feng Li; Daniel Fitz; Donald G. Fraser; Bernd M. Rode (pp. 287-294).

The salt-induced peptide formation (SIPF) reaction takes place readily under mild reaction conditions and proceeds via a copper complex. Its ease of reaction and the universality for prebiotic scenarios add weights to the arguments in favour of the importance of peptide and proteins in the tug of war with the RNA world hypothesis. In addition, the SIPF reaction has a preference for l-form amino acids in dipeptide formation, casting light on the puzzle of biohomochirality, especially for the amino acids with aliphatic side chains. A detailed investigation on the behaviour of aliphatic leucine in the SIPF reaction is presented in this paper, including the catalytic effects of glycine, l- and d-histidine as well as the stereoselectivity under all the reaction conditions above. The results show a relatively low reactivity and stereoselectivity of leucine in the SIPF reaction, while both glycine and histidine enantiomers remarkably increase the yields of dileucine by factors up to 40. Moreover, a comparative study of the effectiveness of l- and d-histidine in catalysing the formation of dimethionine was also carried out and extends the scope of mutual catalysis by amino acid enantiomers in the SIPF reaction.

Keywords: Salt-induced peptide formation reaction; Prebiotic chemistry; Leucine dipeptide; Copper complex with amino acids; Homochirality

Polarized spectroscopic elucidation of N-acetyl-l-cysteine, l-cysteine, l-cystine, l-ascorbic acid and a tool for their determination in solid mixtures by Bojidarka Koleva; Michael Spiteller; Tsonko Kolev (pp. 295-304).

Method of linear polarized vibrational (both IR- and Raman) spectroscopy of oriented colloids in nematic host is applied on N-acetyl-l-cysteine, l-cysteine, l-cystine and l-ascorbic acid with a view to obtain experimental bands assignment and local structural elucidation in solid-state. Structural results are compared with available crystallographic data for all of the systems studied. Scopes and limitations of the polarized method are shown. Discussion on the correlation between polarized spectroscopic data and the space group type as well as the number of the molecules in the unit cell (Z) is performed. Compounds with monoclinic space group P2₁, containing Z = 1 (N-acetyl-l-cysteine) and 2 (l-cysteine and l-ascorbic acid) are elucidated. One of the rare for organic molecules, hexagonal P6₁22 space group and Z = 6 (l-cystine) is also elucidated. Experimental assignment of the characteristics frequencies is obtained, explaining the typical for the crystals Fermi-resonance, Fermy–Davydov and Davydov splitting effects. For first time in the literature we are reported the orientation of the solid-mixture in nematic host, using the trade product ACC (Hexal, Germany), containing mainly N-acetyl-l-cysteine and l-ascorbic acid. Quantitative IR-spectroscopic approach for determination of solid mixtures is presented as well. The intensity ratio between 1,716 cm⁻¹ (characteristic for N-acetyl-l-cysteine) and 990 cm⁻¹, (attributed N-acethyl-cysteine and vitamin C) is used. Linear regression analysis between content and the peak ratio data for ten solid-binary mixtures, leads to straight-line plot y = 1.08₂ (±0.04₉) + (−0.11₄ ± 0.01₁)x, where x = 1/X i. Factor r of 0.9641 and a reliability of 98.85% are obtained. The analysis of ACC 200 (Hexal, Germany) show that the IR measurements leads to standard deviation of 0.010 and 0.011 at P about 0.0500 for the systems and a confidence of >98.77₁%.

Keywords: N-Acetyl-l-cysteine; l-Cysteine; l-Cystine and l-ascorbic acid; IR-LD spectroscopy; Raman spectroscopy; Determination and analysis of solid mixtures

Novel sulfur and selenium containing bis-α-amino acids from 4-hydroxyproline by Romualdo Caputo; Marina DellaGreca; Ivan de Paola; Domenico Mastroianni; Luigi Longobardo (pp. 305-310).

The synthesis of new substituted prolines carrying at C-4 a second α-amino acid residue is reported. The amino acid, l-cysteine or l-selenocysteine, is linked to the proline ring through the sulfur or the selenium atom, respectively. The products were prepared with different stereochemistry at C-4, in few and clean high-yielding steps, with suitable protections for solid phase applications. The introduction of both sulfur and selenium atoms at C-4 of the proline ring seems to enhance significantly the cis geometry at the prolyl amide bond.

Keywords: 4-Substituted proline; Cysteine thioalkylation; Selenocystine; Bis-α-amino acids; Unnatural amino acids

Changes in plasma amino acid levels in a euryhaline fish exposed to different environmental salinities by Cláudia Aragão; Benjamín Costas; Luis Vargas-Chacoff; Ignacio Ruiz-Jarabo; Maria Teresa Dinis; Juan Miguel Mancera; Luís E. C. Conceição (pp. 311-317).

Previous studies have shown that Senegalese sole is partially euryhaline in the juvenile phase, being able to adapt to a wide range of salinities in a short-time period, due to changes at the osmoregulatory and metabolic level. This study aimed to assess the effects of acclimation of sole to a wide range of salinities, with a special emphasis on the role of plasma amino acids during this process. Sole juveniles were acclimated for 2 weeks to different salinities: 5, 15, 25, 38, and 55 g L⁻¹. Plasma levels of cortisol, glucose, osmolality, and free amino acids were assessed at the end. Changes in plasma levels of cortisol, glucose, and amino acids indicate that fish reared at 5 and 55 g L⁻¹ were facing extra energy costs. Amino acids seem to play an important role during salinity acclimation, either as energy sources or as important osmolytes for cell volume regulation.

Keywords: Salinity acclimation; Stress; Amino acids; Osmoregulation; Solea senegalensis

Quantum chemical investigation of nitrotyrosine (3-nitro-l-tyrosine) and 8-nitroguanine by Şakir Erkoç; Figen Erkoç; Aylin Sepici-Dinçel (pp. 319-327).

The structural, vibrational and electronic properties of nitrotyrosine and 8-nitroguanine have been investigated theoretically by performing the molecular mechanics (MM+ force field), the semi-empirical self-consistent-field molecular-orbital (PM3), and density functional theory calculations. The geometry of the nitrotyrosine and 8-nitroguanine molecules have been optimized, the vibrational dynamics and the electronic properties calculated in their ground states in the gas phase.

Keywords: Nitrotyrosine; 8-Nitroguanine; Semiempirical calculations; Ab initio calculations; Density functional calculations

Cyclic DGR-peptidomimetic containing a bicyclic reverse turn inducer as a selective α_vβ₅ integrin ligand by A. Trabocchi; G. Menchi; E. Danieli; D. Potenza; N. Cini; A. Bottoncetti; S. Raspanti; A. Pupi; Antonio Guarna (pp. 329-337).

3-Aza-6,8-dioxabicyclo[3.2.1]octane-based amino acids as reverse turn inducers have been introduced into cyclic peptidomimetics containing the RGD or DGR retro-sequence, in order to achieve a stereochemical scanning of the binding capability of the resulting molecules towards α_vβ₃ and α_vβ₅ integrins, resulting in retro-inverso DGR peptides as micromolar ligands. A comparative analysis between the conformational preferences of 4 and of its isomer 3, having the opposite RGD sequence, was reported with respect to the binding activity, giving insight into the factors affecting the preferential binding of 4 to the α_vβ₅ integrin.

Keywords: Amino acids; Peptides; Peptidomimetics; Bicyclic compounds; Conformational analysis

Effect of l-arginine on metabolism of polyamines in rat’s brain with extrahepatic cholestasis by Dušan Sokolovic; Gordana Bjelakovic; Jelenka Nikolic; Boris Djindjic; Dusica Pavlovic; Gordana Kocic; Ivana Stojanovic; Voja Pavlovic (pp. 339-345).

Cholestatic encephalopathy results from accumulation of unconjugated bilirubin and hydrophobic bile acids in the brain. The aim of this study was to determine disturbances of polyamine metabolism in the brains of rats with experimental extrahepatic cholestasis and the effects of l-arginine administration. Wister rats were divided into groups: I: sham-operated, II: rats treated with l-arginine, III: animals with bile-duct ligation (BDL), and IV: cholestatic-BDL rats treated with l-arginine. Increased plasma γ-glutamyltransferase and alkaline phosphatase activity and increased bile-acids and bilirubin levels in BDL rats were reduced by administration of l-arginine (P < 0.001). Cholestasis increased the brain’s putrescine (P < 0.001) and decreased spermidine and spermine concentration (P < 0.05). The activity of polyamine oxidase was increased (P < 0.001) and diamine oxidase was decreased (P < 0.001) in the brains of BDL rats. Cholestasis increased the activity of arginase (P < 0.05) and decreased the level of citrulline (P < 0.001). Administration of l-arginine in BDL rats prevents metabolic disorders of polyamines and establishs a neuroprotective role in the brain during cholestasis.

Keywords: Polyamines; Cholestasis; l-Arginine; Brain

Predicting protein subcellular location: exploiting amino acid based sequence of feature spaces and fusion of diverse classifiers by Asifullah Khan; Abdul Majid; Tae-Sun Choi (pp. 347-350).

A novel approach CE-Ploc is proposed for predicting protein subcellular locations by exploiting diversity both in feature and decision spaces. The diversity in a sequence of feature spaces is exploited using hydrophobicity and hydrophilicity of amphiphilic pseudo amino acid composition and a specific learning mechanism. Diversity in learning mechanisms is exploited by fusion of classifiers that are based on different learning mechanisms. Significant improvement in prediction performance is observed using jackknife and independent dataset tests.

Keywords: Amphiphilic pseudo amino acid composition; Protein subcellular location; Ensemble classifier

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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.38, #1)