Engineering β-sheet peptide assemblies for biomedical applications

Yu, Zhiqiang; Cai, Zheng; Chen, Qiling; Liu, Menghua; Ye, Ling; Ren, Jiaoyan; Liao, Wenzhen; Liu, Shuwen

doi:10.1039/c5bm00472a

Cited by 83 publications

(48 citation statements)

References 103 publications

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“…The development of biomaterials derived from self‐assembled peptides is of great current interest due to biomedical applications including controlled release drug delivery, vaccine development, tissue engineering, and wound healing . Amphipathic peptides that consist of alternating hydrophobic and hydrophilic amino acids are a privileged class of peptide that readily self‐assembles into β‐sheet bilayer nanoribbons that share the basic characteristics of cross‐β amyloid assemblies (Figure ) .…”

Section: Introductionmentioning

confidence: 99%

Balancing hydrophobicity and sequence pattern to influence self‐assembly of amphipathic peptides

2018

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Amphipathic peptides with alternating polar and nonpolar amino acid sequences efficiently selfassemble into functional b-sheet fibrils as long as the nonpolar residues have sufficient hydrophobicity. For example, the Ac-(FKFE) 2 -NH 2 peptide rapidly self-assembles into b-sheet bilayer nanoribbons, while Ac-(AKAE) 2 -NH 2 fails to self-assemble under similar conditions due to the significantly reduced hydrophobicity and b-sheet propensity of Ala relative to Phe. Herein, we systematically explore the effect of substituting only two of the four Ala residues at various positions in the Ac-(AKAE) 2 -NH 2 peptide with amino acids of increasing hydrophobicity, b-sheet potential, and surface area (including Phe, 1-naphthylalanine (1-Nal), 2-naphthylalanine (2-Nal), cyclohexylalanine (Cha), and pentafluorophenylalanine (F 5 -Phe)) on the self-assembly propensity of the resulting sequences. It was found that double Phe variants, regardless of the position of substitution, failed to self-assemble under the conditions used in this study. In contrast, all double 1-Nal and 2-Nal variants readily self-assembled, albeit at differing rates depending on the substitution patterns. To determine whether this was due to hydrophobicity or side chain surface area, we also prepared double Cha and F 5 -Phe variant peptides (both side chain groups are more hydrophobic than Phe). Each of these variants also underwent effective self-assembly, with the aromatic F 5 -Phe peptides doing so with greater efficiency. These findings provide insight into the role of amino acid hydrophobicity and sequence pattern on self-assembly proclivity of amphipathic peptides and on how targeted substitutions of nonpolar residues in these sequences can be exploited to tune the characteristics of the resulting self-assembled materials.hydrophobicity, peptide, self-assembly | I N TR ODU C TI ONThe development of biomaterials derived from self-assembled peptides is of great current interest due to biomedical applications including controlled release drug delivery, vaccine development, tissue engineering, and wound healing. Amphipathic peptides that consist of alternating hydrophobic and hydrophilic amino acids are a privileged class of peptide that readily self-assembles into b-sheet bilayer nanoribbons that share the basic characteristics of cross-b amyloid assemblies (Figure 1). [23][24][25][26][27][28][29][30] These bilayer nanoribbons effectively sequester all hydrophobic functionality to the bilayer interior, leaving hydrophilic groups exposed to solvent on the exterior face. [24,[31][32][33][34] As a result, these nanoribbons maintain high solubility in aqueous solvents, making them ideal materials for biological applications. Because of the high utility of this class of amphipathic peptide, they have been widely adopted as models to study the fundamental physicochemical basis of peptide self-assembly processes in order to facilitate the rational design of next-generation materials derived from self-assembled b-sheet peptides.[ [35][36][37][38][39]...

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Section: Introductionmentioning

confidence: 99%

Balancing hydrophobicity and sequence pattern to influence self‐assembly of amphipathic peptides

2018

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“…Custom molecular structures can be designed and synthesized through tuning the peptide basic units. Naturally occurring structures occurred in proteins such as -helices and -sheets that can be utilized for driving the self-assembly processes [20][21][22]. Moreover, the self-assembly process is also very important in the functions of cell-penetrating peptides that could play an important role in delivering the drugs inside the cell membrane and transporting genes into the nucleus [23].…”

Section: Introductionmentioning

confidence: 99%

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Fan

Shen

et al. 2017

Journal of Nanomaterials

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Peptide self-assembled nanostructures are very popular in many biomedical applications. Drug delivery is one of the most promising applications among them. The tremendous advantages for peptide self-assembled nanostructures include good biocompatibility, low cost, tunable bioactivity, high drug loading capacities, chemical diversity, specific targeting, and stimuli responsive drug delivery at disease sites. Peptide self-assembled nanostructures such as nanoparticles, nanotubes, nanofibers, and hydrogels have been investigated by many researchers for drug delivery applications. In this review, the underlying mechanisms for the self-assembled nanostructures based on peptides with different types and structures are introduced and discussed. Peptide self-assembled nanostructures associated promising drug delivery applications such as anticancer drug and gene drug delivery are highlighted. Furthermore, peptide self-assembled nanostructures for targeted and stimuli responsive drug delivery applications are also reviewed and discussed.

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“…While their use may be an acceptable short-term risk for acute conditions, the long-term relief of localized chronic diseases would benefit greatly from alternative approaches. One method is the use of in situ hydrogels, either polymer or supramolecular-based, as localized drug depots30-38. The study of these systems has attracted increasing attention due to their abundant advantages in drug administration, including ease of preparation, biocompatibility, convenience and improved patient compliance, high regional drug concentration and low systemic toxicity34, 39-44.…”

Section: Introductionmentioning

confidence: 99%

Drug-Bearing Supramolecular Filament Hydrogels as Anti-Inflammatory Agents

et al. 2017

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We report here on the covalent conversion of the anti-inflammatory agent ketoprofen into self-assembling prodrugs that enable the effective purification of ketoprofen enantiomers, the improved selectivity and potency of ketoprofen, as well as the formation of one-component drug-bearing supramolecular hydrogels. We found that the ketoprofen hydrogelator could exhibit much-enhanced selectivity for cyclooxygenase 2 (COX-2) over COX-1, reduce the concentration of inflammatory cytokines (IL-1 and TNFα), and induce apoptosis in fibroblast-like synoviocytes while maintaining biocompatibility with healthy chondrocytes. In addition, these anti-inflammatory agent-containing hydrogels demonstrated the ability to retain the therapeutic within a joint cavity after intra-articular injection, exhibiting a slow, steady release into the plasma. We believe that upon further optimization these drug-based injectable supramolecular hydrogels could provide the basis for a local treatment strategy for rheumatoid arthritis and similar conditions.

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Engineering β-sheet peptide assemblies for biomedical applications

Cited by 83 publications

References 103 publications

Balancing hydrophobicity and sequence pattern to influence self‐assembly of amphipathic peptides

Balancing hydrophobicity and sequence pattern to influence self‐assembly of amphipathic peptides

Peptide Self-Assembled Nanostructures for Drug Delivery Applications

Drug-Bearing Supramolecular Filament Hydrogels as Anti-Inflammatory Agents

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