The unexpected advantages of using D-amino acids for peptide self-assembly into nanostructured hydrogels for medicine

Melchionna, Michele; Styan, Katie; Marchesan, Silvia

doi:10.2174/1568026616666160215155136

Cited by 4 publications

(3 citation statements)

References 35 publications

(44 reference statements)

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“…Recent work by H. Hirt et al suggests that protease-resistance is not the only difference on killing effectiveness of E. faecalis between L- and D-enantiomers of AMPs 25 . Structural differences between L- and D-enantiomers of the same peptide have been scarcely explored 27 , mainly because identical mirrored structures between the two enantiomers are expected. However, recent work has noted that peptide chirality induces differences in the molecular structure and self-assembly of peptides in solution.…”

Section: Introductionmentioning

confidence: 99%

Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

Zhu

Acosta

et al. 2019

Nanoscale

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Recent studies have shown that antimicrobial peptides (AMPs) can self-assemble into supramolecular structures, but this has been overlooked as causative of their antimicrobial activity. Also, the higher antimicrobial potency of D-enantiomers compared to L-enantiomers of AMPs cannot always be attributed to their different resistance to protease degradation. Here, we tested all L- and D-amino acid versions of GL13K, an AMP derived from a human protein, to study structural links between AMPs secondary structure, supramolecular self-assembly dynamics, and antimicrobial activity. pH dependence and the evolution of secondary structures were related to a self-assembling process with differences among these AMPs. The two GL13K enantiomers formed analogous self-assembled twisted nanoribbon structures, but D-GL13K initiated self-assembly faster and had notably higher antimicrobial potency than L-GL13K. A non-antimicrobial scrambled amino acid version of LGL13K assembled at a much higher pH to form distinctively different self-assembled structures than L-GL13K. Our results support a functional relationship between the AMPs self-assembly and their antimicrobial activity.

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Section: Introductionmentioning

confidence: 99%

Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

Zhu

Acosta

et al. 2019

Nanoscale

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“…Peptide hydrogels can also be utilized for other applications, such as sensing, catalysis, and optoelectronics, in which they act as structural scaffolds or directly perform desired functions . Yet, the application of peptide hydrogels is still limited in many cases due to poor or marginally tunable rheological properties, lack of enzymatic stability, and absence of multifunctionality . Moreover, in the process of generating application‐specific functionalities by mutating the amino acid sequence, the mechanical properties of peptide hydrogels may become impaired .…”

mentioning

confidence: 99%

Expanding the Functional Scope of the Fmoc‐Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

et al. 2019

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Peptidomimetic low‐molecular‐weight hydrogelators, a class of peptide‐like molecules with various backbone amide modifications, typically give rise to hydrogels of diverse properties and increased stability compared to peptide hydrogelators. Here, a new peptidomimetic low‐molecular‐weight hydrogelator is designed based on the well‐studied N ‐fluorenylmethoxycarbonyl diphenylalanine (Fmoc‐FF) peptide by replacing the amide bond with a frequently employed amide bond surrogate, the urea moiety, aiming to increase hydrogen bonding capabilities. This designed ureidopeptide, termed Fmoc—Phe—NHCONH—Phe—OH (Fmoc‐FuF), forms hydrogels with improved mechanical properties, as compared to those formed by the unmodified Fmoc‐FF. A combination of experimental and computational structural methods shows that hydrogen bonding and aromatic interactions facilitate Fmoc‐FuF gel formation. The Fmoc‐FuF hydrogel possesses properties favorable for biomedical applications, including shear thinning, self‐healing, and in vitro cellular biocompatibility. Additionally, the Fmoc‐FuF, but not Fmoc‐FF, hydrogel presents a range of functionalities useful for other applications, including antifouling, slow release of urea encapsulated in the gel at a high concentration, selective mechanical response to fluoride anions, and reduction of metal ions into catalytic nanoparticles. This study demonstrates how a simple backbone modification can enhance the mechanical properties and functional scope of a peptide hydrogel.

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“…Such modular designs will offer infinite opportunities to modulate conformation, expanding the range of possible applications and fine-tuning the properties of resulting hydrogels. Incorporation of noncanonical amino acids in peptides could be an alternating strategy to form ordered supramolecular hydrogels which are biostable and can be suitable for long-term applications. − One such class being the γ-amino acids or double-homologated α-amino acids. These homologated backbones confer additional conformational flexibility compared to their parent α-amino acids.…”

Section: Introductionmentioning

confidence: 99%

Conformation Controlled Hydrogelation of Minimalistic α, γ Hybrid Peptide

Dasgupta,

Sen,

Sathe

et al. 2024

Biomacromolecules

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A majority of short peptide (≤7 amino acids) hydrogels are primarily assembled via cross β-structure formation. In contrast to the natural trend, herein, we report the formation of supramolecular hydrogel from the ultrashort hybrid folded peptide composed of canonical α-amino acid and noncanonical γ-amino acid, Fmoc-γPhe-Phe-OH. The designed hybrid peptide hydrogel is composed of entangled fibers, has viscoelastic properties, exhibits proteolytic stability, and exhibits cytocompatibility with L929 fibroblast cells. Mutating the peptide sequence by altering the position of γPhe from the N-termini to C-termini transforms the self-assembly into crystalline aggregates. Combining FTIR, 2D NMR, and DFT calculations revealed that the hydrogel-forming peptide adopts a C9 H-bonded conformation, resembling the well-known γ-turn. However, the isomeric hybrid peptide adopts an extended structure. The present study highlights the importance of secondary structure in the higher order assembly of minimalist hybrid peptides and broadens the range of secondary structures to design short peptide-based hydrogels.

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The unexpected advantages of using D-amino acids for peptide self-assembly into nanostructured hydrogels for medicine

Cited by 4 publications

References 35 publications

Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

Self-assembly dynamics and antimicrobial activity of all l- and d-amino acid enantiomers of a designer peptide

Expanding the Functional Scope of the Fmoc‐Diphenylalanine Hydrogelator by Introducing a Rigidifying and Chemically Active Urea Backbone Modification

Conformation Controlled Hydrogelation of Minimalistic α, γ Hybrid Peptide

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