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Advanced Drug Delivery Reviews (v.62, #15)
Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery
by Dan W. Urry; Kelley D. Urry; Witold Szaflarski; Michal Nowicki (pp. 1404-1455).
This review presents the structure and physico-chemical properties of ECMPs, elastic-contractile model proteins using sparse design modifications of elastic (GVGVP)n; it describes the capacity of ECMP to perform the energy conversions that sustain living organisms; it arrives at the hydration thermodynamics of ECMP in terms of the change in Gibbs free energy of hydrophobic association,ΔGHA, and the apolar–polar repulsive free energy of hydration, ΔGap; it appliesΔGHA, ΔGap, and the nature of elasticity to describe the function of basic diverse proteins, namely — the F1-motor of ATP synthase, Complex III of mitochondria, the KscA potassium-channel, and the molecular chaperonin, GroEL/ES; it appliesΔGHA and ΔGap to describe the function of ABC exporter proteins that confer multi-drug resistance (MDR) on micro-organisms and human carcinomas and suggests drug modifications with which to overcome MDR. Using ECMP, means are demonstrated, for quantifying drug hydrophobicity with which to combat MDR and for preparing ECMP drug delivery nanoparticles, ECMPddnp, decorated with synthetic antigen-binding fragments, Fab1 and Fab2, with which to target specific up-regulated receptors, characteristic of human carcinoma cells, for binding and localized drug release.
Keywords: Elastic-contractile model proteins; Gibbs free energy(hydrophobic association); Elasticity of (GVGVP); n; Multi-drug resistance (MDR); Drug-laden nanoparticles; Antigen binding fragments Fab1/Fab2
Elastic-contractile model proteins: Physical chemistry, protein function and drug design and delivery
by Dan W. Urry; Kelley D. Urry; Witold Szaflarski; Michal Nowicki (pp. 1404-1455).
This review presents the structure and physico-chemical properties of ECMPs, elastic-contractile model proteins using sparse design modifications of elastic (GVGVP)n; it describes the capacity of ECMP to perform the energy conversions that sustain living organisms; it arrives at the hydration thermodynamics of ECMP in terms of the change in Gibbs free energy of hydrophobic association,ΔGHA, and the apolar–polar repulsive free energy of hydration, ΔGap; it appliesΔGHA, ΔGap, and the nature of elasticity to describe the function of basic diverse proteins, namely — the F1-motor of ATP synthase, Complex III of mitochondria, the KscA potassium-channel, and the molecular chaperonin, GroEL/ES; it appliesΔGHA and ΔGap to describe the function of ABC exporter proteins that confer multi-drug resistance (MDR) on micro-organisms and human carcinomas and suggests drug modifications with which to overcome MDR. Using ECMP, means are demonstrated, for quantifying drug hydrophobicity with which to combat MDR and for preparing ECMP drug delivery nanoparticles, ECMPddnp, decorated with synthetic antigen-binding fragments, Fab1 and Fab2, with which to target specific up-regulated receptors, characteristic of human carcinoma cells, for binding and localized drug release.
Keywords: Elastic-contractile model proteins; Gibbs free energy(hydrophobic association); Elasticity of (GVGVP); n; Multi-drug resistance (MDR); Drug-laden nanoparticles; Antigen binding fragments Fab1/Fab2
Drug delivery to solid tumors by elastin-like polypeptides
by Jonathan R. McDaniel; Daniel J. Callahan; Ashutosh Chilkoti (pp. 1456-1467).
Thermally responsive elastin-like polypeptides (ELPs) are a promising class of recombinant biopolymers for the delivery of drugs and imaging agents to solid tumors via systemic or local administration. This article reviews four applications of ELPs to drug delivery, with each delivery mechanism designed to best exploit the relationship between the characteristic transition temperature ( Tt) of the ELP and body temperature ( Tb). First, when Tt≫ Tb, small hydrophobic drugs can be conjugated to the C-terminus of the ELP to impart the amphiphilicity needed to mediate the self-assembly of nanoparticles. These systemically delivered ELP–drug nanoparticles preferentially localize to the tumor site via the EPR effect, resulting in reduced toxicity and enhanced treatment efficacy. The remaining three approaches take direct advantage of the thermal responsiveness of ELPs. In the second strategy, where Tb< Tt<42°C, an ELP–drug conjugate can be injected in conjunction with external application of mild hyperthermia to the tumor to induce ELP coacervation and an increase in concentration within the tumor vasculature. The third approach utilizes hydrophilic–hydrophobic ELP block copolymers that have been designed to assemble into nanoparticles in response to hyperthermai due to the independent thermal transition of the hydrophobic block, thus resulting in multivalent ligand display of a ligand for spatially enhanced vascular targeting. In the final strategy, ELPs with Tt< Tb are conjugated with radiotherapeutics, injtect intioa tumor where they undergo coacervation to form an injectable drug depot for intratumoral delivery. These injectable coacervate ELP-radionuclide depots display a long residence in the tumor and result in inhibition of tumor growth.
Keywords: Elastin-like polypeptide; Biopolymer; Hyperthermia; Thermally responsive polymer; pH-controlled release; Lower critical solution temperature; Cancer therapy; Micelles
Drug delivery to solid tumors by elastin-like polypeptides
by Jonathan R. McDaniel; Daniel J. Callahan; Ashutosh Chilkoti (pp. 1456-1467).
Thermally responsive elastin-like polypeptides (ELPs) are a promising class of recombinant biopolymers for the delivery of drugs and imaging agents to solid tumors via systemic or local administration. This article reviews four applications of ELPs to drug delivery, with each delivery mechanism designed to best exploit the relationship between the characteristic transition temperature ( Tt) of the ELP and body temperature ( Tb). First, when Tt≫ Tb, small hydrophobic drugs can be conjugated to the C-terminus of the ELP to impart the amphiphilicity needed to mediate the self-assembly of nanoparticles. These systemically delivered ELP–drug nanoparticles preferentially localize to the tumor site via the EPR effect, resulting in reduced toxicity and enhanced treatment efficacy. The remaining three approaches take direct advantage of the thermal responsiveness of ELPs. In the second strategy, where Tb< Tt<42°C, an ELP–drug conjugate can be injected in conjunction with external application of mild hyperthermia to the tumor to induce ELP coacervation and an increase in concentration within the tumor vasculature. The third approach utilizes hydrophilic–hydrophobic ELP block copolymers that have been designed to assemble into nanoparticles in response to hyperthermai due to the independent thermal transition of the hydrophobic block, thus resulting in multivalent ligand display of a ligand for spatially enhanced vascular targeting. In the final strategy, ELPs with Tt< Tb are conjugated with radiotherapeutics, injtect intioa tumor where they undergo coacervation to form an injectable drug depot for intratumoral delivery. These injectable coacervate ELP-radionuclide depots display a long residence in the tumor and result in inhibition of tumor growth.
Keywords: Elastin-like polypeptide; Biopolymer; Hyperthermia; Thermally responsive polymer; pH-controlled release; Lower critical solution temperature; Cancer therapy; Micelles
Recombinant elastin-mimetic biomaterials: Emerging applications in medicine
by Wookhyun Kim; Elliot L. Chaikof (pp. 1468-1478).
Biomaterials derived from protein-based block copolymers are increasingly investigated for potential application in medicine. In particular, recombinant elastin block copolymers provide significant opportunities to modulate material microstructure and can be processed in various forms, including particles, films, gels, and fiber networks. As a consequence, biological and mechanical responses of elastin-based biomaterials are tunable through precise control of block size and amino acid sequence. In this review, the synthesis of a set of elastin-mimetic triblock copolymers and their diverse processing methods for generating material platforms currently applied in medicine will be discussed.
Keywords: Biomaterials; Block copolymers; Drug delivery; Implant; Biocompatibility
Recombinant elastin-mimetic biomaterials: Emerging applications in medicine
by Wookhyun Kim; Elliot L. Chaikof (pp. 1468-1478).
Biomaterials derived from protein-based block copolymers are increasingly investigated for potential application in medicine. In particular, recombinant elastin block copolymers provide significant opportunities to modulate material microstructure and can be processed in various forms, including particles, films, gels, and fiber networks. As a consequence, biological and mechanical responses of elastin-based biomaterials are tunable through precise control of block size and amino acid sequence. In this review, the synthesis of a set of elastin-mimetic triblock copolymers and their diverse processing methods for generating material platforms currently applied in medicine will be discussed.
Keywords: Biomaterials; Block copolymers; Drug delivery; Implant; Biocompatibility
Applications of elastin-like polypeptides in tissue engineering
by Dana L. Nettles; Ashutosh Chilkoti; Lori A. Setton (pp. 1479-1485).
Elastin-like polypeptides (ELPs) have found utility in tissue engineering applications, not only because they are biocompatible, biodegradable, and non-immunogenic, but also because their amino acid sequence and molecular weight can be precisely controlled at the genetic or synthetic level, affording exquisite control over final protein functionality. This review presents a basic overview of ELP properties and modifications that are relevant to tissue engineering, as well as a discussion of the application of ELPs to cartilage, intervertebral disc, vascular graft, liver, ocular, and cell sheet engineering.
Keywords: Hydrogel; Tissue engineering; Cartilage; Liver; Elastin; Crosslinking; Vascular graft
Applications of elastin-like polypeptides in tissue engineering
by Dana L. Nettles; Ashutosh Chilkoti; Lori A. Setton (pp. 1479-1485).
Elastin-like polypeptides (ELPs) have found utility in tissue engineering applications, not only because they are biocompatible, biodegradable, and non-immunogenic, but also because their amino acid sequence and molecular weight can be precisely controlled at the genetic or synthetic level, affording exquisite control over final protein functionality. This review presents a basic overview of ELP properties and modifications that are relevant to tissue engineering, as well as a discussion of the application of ELPs to cartilage, intervertebral disc, vascular graft, liver, ocular, and cell sheet engineering.
Keywords: Hydrogel; Tissue engineering; Cartilage; Liver; Elastin; Crosslinking; Vascular graft
Cell penetrating elastin-like polypeptides for therapeutic peptide delivery
by Gene L. Bidwell III; Drazen Raucher (pp. 1486-1496).
Current treatment of solid tumors is limited by side effects that result from the non-specific delivery of drugs to the tumor site. Alternative targeted therapeutic approaches for localized tumors would significantly reduce systemic toxicity. Peptide therapeutics are a promising new strategy for targeted cancer therapy because of the ease of peptide design and the specificity of peptides for their intracellular molecular targets. However, the utility of peptides is limited by their poor pharmacokinetic parameters and poor tissue and cellular membrane permeability in vivo. This review article summarizes the development of elastin-like polypeptide (ELP) as a potential carrier for thermally targeted delivery of therapeutic peptides (TP), and the use of cell penetrating peptides (CPP) to enhance the intracellular delivery of the ELP-fused TPs. CPP-fused ELPs have been used to deliver a peptide inhibitor of c-Myc function and a peptide mimetic of p21 in several cancer models in vitro, and both polypeptides are currently yielding promising results in in vivo models of breast and brain cancer.
Keywords: Elastin-like polypeptide; Thermal targeting; Therapeutic peptide; Cell penetrating peptide; c-Myc; p21
Cell penetrating elastin-like polypeptides for therapeutic peptide delivery
by Gene L. Bidwell III; Drazen Raucher (pp. 1486-1496).
Current treatment of solid tumors is limited by side effects that result from the non-specific delivery of drugs to the tumor site. Alternative targeted therapeutic approaches for localized tumors would significantly reduce systemic toxicity. Peptide therapeutics are a promising new strategy for targeted cancer therapy because of the ease of peptide design and the specificity of peptides for their intracellular molecular targets. However, the utility of peptides is limited by their poor pharmacokinetic parameters and poor tissue and cellular membrane permeability in vivo. This review article summarizes the development of elastin-like polypeptide (ELP) as a potential carrier for thermally targeted delivery of therapeutic peptides (TP), and the use of cell penetrating peptides (CPP) to enhance the intracellular delivery of the ELP-fused TPs. CPP-fused ELPs have been used to deliver a peptide inhibitor of c-Myc function and a peptide mimetic of p21 in several cancer models in vitro, and both polypeptides are currently yielding promising results in in vivo models of breast and brain cancer.
Keywords: Elastin-like polypeptide; Thermal targeting; Therapeutic peptide; Cell penetrating peptide; c-Myc; p21
Silk-based delivery systems of bioactive molecules
by Keiji Numata; David L. Kaplan (pp. 1497-1508).
Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed.
Keywords: Silk; Recombinant protein; Gene delivery; Drug delivery; Biomaterials; Bioengineering
Silk-based delivery systems of bioactive molecules
by Keiji Numata; David L. Kaplan (pp. 1497-1508).
Silks are biodegradable, biocompatible, self-assembling proteins that can also be tailored via genetic engineering to contain specific chemical features, offering utility for drug and gene delivery. Silkworm silk has been used in biomedical sutures for decades and has recently achieved Food and Drug Administration approval for expanded biomaterials device utility. With the diversity and control of size, structure and chemistry, modified or recombinant silk proteins can be designed and utilized in various biomedical application, such as for the delivery of bioactive molecules. This review focuses on the biosynthesis and applications of silk-based multi-block copolymer systems and related silk protein drug delivery systems. The utility of these systems for the delivery of small molecule drugs, proteins and genes is reviewed.
Keywords: Silk; Recombinant protein; Gene delivery; Drug delivery; Biomaterials; Bioengineering
Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy
by Joshua A. Gustafson; Hamidreza Ghandehari (pp. 1509-1523).
Silk-elastinlike protein polymers (SELPs) are recombinant polymers designed from silk fibroin and mammalian elastin amino acid repeats. These are versatile materials that have been examined as controlled release systems for intratumoral gene delivery. SELP hydrogels comprise monodisperse and tunable polymers that have the capability to control and localize the release and expression of plasmid DNA and viruses. This article reviews recent developments in the synthesis and characterization of SELP hydrogels and their use for matrix-mediated gene delivery.
Keywords: Abbreviations; As(x); Aspartic acid or Asparagine; 3S; 3 silk unit gene monomer; A; Alanine; Ad.HSVtk; Adenovirus carrying herpes simplex virus thymidine kinase gene; Ad.GFP; Adenovirus carrying green fluorescent protein gene; Ad.LacZ; Gene encoding for beta-galactosidase; AFM; Atomic force microscopy; AGR; Albumin/globulin ratio; Ala; Alanine; ALB; Albumin; ALT; Alanine aminotransferase; Arg; Arginine; AST; Aspartate aminotransferase; ATCC; American type culture collection; BCA; Bicinchoninic acid; bp; base pairs; BUN; Blood urea nitrogen; CAR; Coxsackie and adenovirus receptor; CBC; Complete blood count; CGC; Critical gelation concentration; CRE; Creatinine; D; Aspartic Acid; Da; Dalton; DMA; Dynamic mechanical analysis; DNA; Deoxyribonucleic acid; E; Glutamic Acid; FDA; United States Food and Drug Administration; G; Glycine; GCV; Ganciclovir; GDEPT; Gene-directed enzyme-prodrug therapy; GFP; Green fluorescent protein; Gl(x); Glutamic acid or Glutamine; GLOB; Globulin; Gly; Glycine; GRA; Granulocyte; H; Histidine; HCT; Hematocrit; His; Histidine; HNSCC; Head and neck squamous cell carcinoma; HSVtk; Herpes simplex virus thymidine kinase; L; Leucine; Leu; Leucine; LYM; Lymphocyte; Lys; Lysine; M; Methionine; MALDI-TOF; Matrix-assisted laser desorption-ionization-time-of-flight; Met; Methionine; MON; Mononuclear leukocyte; N; Asparagine; P; Proline; PAMAM; Poly (amido amine); PBS; Phosphate buffered saline; PCR; Polymerase chain reaction; PFU; Plaque forming unit; Phe; Phenylalanine; PLT; Platelet; pPT317; Expression vector for production of SELP; pPT340; Plasmid encoding for SELP-415K; Pro; Proline; pSY1378; Plasmid encoding for six silk units; Q; Glutamine; q; Swelling ratio; RBC; Red blood cell; Res/Mol Ob; Observed amino acid residues per mole of protein; Res/Mol Th; Theoretical amino acid residues per mole of protein; RT-PCR; Real-time PCR; S; Serine; SANS; Small-angle neutron scattering; SAP; Shrimp Alkaline Phosphatase; SDS-PAGE; Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; SELP; Silk-elastinlike protein polymer; Ser; Serine; SLP6; Six silk unit monomer; T; Threonine; TBIL; Total bilirubin; Thr; Threonine; TP; Total protein; Trp; Tryptophan; Tyr; Tyrosine; V; Valine; Val; Valine; W; Tryptophan; WBC; White blood cell; Y; Tyrosine; β-gal; Beta-galactosidaseSilk-elastinlike protein polymers; Recombinant polymers; Gene delivery; Viral directed enzyme prodrug therapy; Hydrogels
Silk-elastinlike protein polymers for matrix-mediated cancer gene therapy
by Joshua A. Gustafson; Hamidreza Ghandehari (pp. 1509-1523).
Silk-elastinlike protein polymers (SELPs) are recombinant polymers designed from silk fibroin and mammalian elastin amino acid repeats. These are versatile materials that have been examined as controlled release systems for intratumoral gene delivery. SELP hydrogels comprise monodisperse and tunable polymers that have the capability to control and localize the release and expression of plasmid DNA and viruses. This article reviews recent developments in the synthesis and characterization of SELP hydrogels and their use for matrix-mediated gene delivery.
Keywords: Abbreviations; As(x); Aspartic acid or Asparagine; 3S; 3 silk unit gene monomer; A; Alanine; Ad.HSVtk; Adenovirus carrying herpes simplex virus thymidine kinase gene; Ad.GFP; Adenovirus carrying green fluorescent protein gene; Ad.LacZ; Gene encoding for beta-galactosidase; AFM; Atomic force microscopy; AGR; Albumin/globulin ratio; Ala; Alanine; ALB; Albumin; ALT; Alanine aminotransferase; Arg; Arginine; AST; Aspartate aminotransferase; ATCC; American type culture collection; BCA; Bicinchoninic acid; bp; base pairs; BUN; Blood urea nitrogen; CAR; Coxsackie and adenovirus receptor; CBC; Complete blood count; CGC; Critical gelation concentration; CRE; Creatinine; D; Aspartic Acid; Da; Dalton; DMA; Dynamic mechanical analysis; DNA; Deoxyribonucleic acid; E; Glutamic Acid; FDA; United States Food and Drug Administration; G; Glycine; GCV; Ganciclovir; GDEPT; Gene-directed enzyme-prodrug therapy; GFP; Green fluorescent protein; Gl(x); Glutamic acid or Glutamine; GLOB; Globulin; Gly; Glycine; GRA; Granulocyte; H; Histidine; HCT; Hematocrit; His; Histidine; HNSCC; Head and neck squamous cell carcinoma; HSVtk; Herpes simplex virus thymidine kinase; L; Leucine; Leu; Leucine; LYM; Lymphocyte; Lys; Lysine; M; Methionine; MALDI-TOF; Matrix-assisted laser desorption-ionization-time-of-flight; Met; Methionine; MON; Mononuclear leukocyte; N; Asparagine; P; Proline; PAMAM; Poly (amido amine); PBS; Phosphate buffered saline; PCR; Polymerase chain reaction; PFU; Plaque forming unit; Phe; Phenylalanine; PLT; Platelet; pPT317; Expression vector for production of SELP; pPT340; Plasmid encoding for SELP-415K; Pro; Proline; pSY1378; Plasmid encoding for six silk units; Q; Glutamine; q; Swelling ratio; RBC; Red blood cell; Res/Mol Ob; Observed amino acid residues per mole of protein; Res/Mol Th; Theoretical amino acid residues per mole of protein; RT-PCR; Real-time PCR; S; Serine; SANS; Small-angle neutron scattering; SAP; Shrimp Alkaline Phosphatase; SDS-PAGE; Sodium dodecyl sulfate–polyacrylamide gel electrophoresis; SELP; Silk-elastinlike protein polymer; Ser; Serine; SLP6; Six silk unit monomer; T; Threonine; TBIL; Total bilirubin; Thr; Threonine; TP; Total protein; Trp; Tryptophan; Tyr; Tyrosine; V; Valine; Val; Valine; W; Tryptophan; WBC; White blood cell; Y; Tyrosine; β-gal; Beta-galactosidaseSilk-elastinlike protein polymers; Recombinant polymers; Gene delivery; Viral directed enzyme prodrug therapy; Hydrogels
Development of recombinant cationic polymers for gene therapy research
by Brenda F. Canine; Arash Hatefi (pp. 1524-1529).
Cationic polymers created through recombinant DNA technology have the potential to fill a void in the area of gene delivery. The recombinant cationic polymers to be discussed here are amino acid based polymers synthesized in E. coli with the purpose to not only address the major barriers to efficient gene delivery but offer safety, biodegradability, targetability and cost-effectiveness. This review helps the readers to get a better understanding about the evolution of recombinant cationic polymers; and the potential advantages that they could offer over viral and synthetic non-viral vectors for gene delivery. It also discusses some of the major challenges that must be addressed in future studies to turn recombinant polymers into clinically effective gene delivery systems. Recent advances with the biopolymer design suggest that this emerging new class of gene delivery systems has the potential to address some of the major barriers to efficient, safe and cost-effective gene therapy.
Keywords: Gene delivery; Targeted therapy; Biopolymer; Non-viral; Bioinspired; Fusion peptides; Nanoparticles
Development of recombinant cationic polymers for gene therapy research
by Brenda F. Canine; Arash Hatefi (pp. 1524-1529).
Cationic polymers created through recombinant DNA technology have the potential to fill a void in the area of gene delivery. The recombinant cationic polymers to be discussed here are amino acid based polymers synthesized in E. coli with the purpose to not only address the major barriers to efficient gene delivery but offer safety, biodegradability, targetability and cost-effectiveness. This review helps the readers to get a better understanding about the evolution of recombinant cationic polymers; and the potential advantages that they could offer over viral and synthetic non-viral vectors for gene delivery. It also discusses some of the major challenges that must be addressed in future studies to turn recombinant polymers into clinically effective gene delivery systems. Recent advances with the biopolymer design suggest that this emerging new class of gene delivery systems has the potential to address some of the major barriers to efficient, safe and cost-effective gene therapy.
Keywords: Gene delivery; Targeted therapy; Biopolymer; Non-viral; Bioinspired; Fusion peptides; Nanoparticles
Multivalent protein polymers with controlled chemical and physical properties
by Ayben Top; Kristi L. Kiick (pp. 1530-1540).
In this review, we describe our work on the design, characterization, and modification of a series of alanine-rich helical polypeptides with novel functions. Glycosylation of the polypeptides has permitted investigation of polymer architecture effects on multivalent interactions. One of the members of this polypeptide family exhibits polymorphological behavior that is easily manipulated via simple changes in solution pH and temperature. Polypeptide-based fibrils formed at acidic pH and high temperature were shown to direct the one-dimensional organization of gold nanoparticles via electrostatic interactions. As a precursor to fibrils, aggregates likely comprising alanine-rich cores form at low temperatures and acidic pH and reversibly dissociate into monomers upon deprotonation. PEGylation of these polypeptides does not alter the self-association or conformational behavior of the polypeptide, suggesting potential applications in the development of assembled delivery vehicles, as modification of the polypeptides should be a useful strategy for controlling assembly.
Keywords: Polypeptide; Biosynthesis; Self-assembly; Fibril; Multivalent interactions; Nanostructure; PEGylation; Glycopolymer; Nanoparticle array
Multivalent protein polymers with controlled chemical and physical properties
by Ayben Top; Kristi L. Kiick (pp. 1530-1540).
In this review, we describe our work on the design, characterization, and modification of a series of alanine-rich helical polypeptides with novel functions. Glycosylation of the polypeptides has permitted investigation of polymer architecture effects on multivalent interactions. One of the members of this polypeptide family exhibits polymorphological behavior that is easily manipulated via simple changes in solution pH and temperature. Polypeptide-based fibrils formed at acidic pH and high temperature were shown to direct the one-dimensional organization of gold nanoparticles via electrostatic interactions. As a precursor to fibrils, aggregates likely comprising alanine-rich cores form at low temperatures and acidic pH and reversibly dissociate into monomers upon deprotonation. PEGylation of these polypeptides does not alter the self-association or conformational behavior of the polypeptide, suggesting potential applications in the development of assembled delivery vehicles, as modification of the polypeptides should be a useful strategy for controlling assembly.
Keywords: Polypeptide; Biosynthesis; Self-assembly; Fibril; Multivalent interactions; Nanostructure; PEGylation; Glycopolymer; Nanoparticle array
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