The substitution of a single amino acid with its enantiomer for control over the adjuvant activity of self-assembling peptides

Li, Mingyu; Liu, Mingyuan; Shang, Yuna; Ren, Chunhua; Liu, Jianfeng; Jin, Honglin; Wang, Zhongyan

doi:10.1039/c9ra10325b

Cited by 7 publications

(3 citation statements)

References 39 publications

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“…Our choice of heterochiral sequences was dictated by the observation that introducing d -amino acids at selected positions has proven successful as a strategy to achieve hydrogels from uncapped tripeptides. , In this manner, it is possible to orient favorably the side chains of hydrophobic sequences to access amphiphilic gelling structures, as was recently reviewed . Heterochirality is gaining momentum as a strategy to tailor peptide self-assembly. − Uncapped dipeptides are very attractive building blocks due to their chemical simplicity. Furthermore, enantiomers are expected to display the same self-assembly behavior in achiral environments, therefore, investigation of compounds 2 – 6 will shed light also on the self-assembly of their mirror-image l - d dipeptide isomers.…”

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confidence: 99%

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

et al. 2020

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Diphenylalanine is an amyloidogenic building block that can form a versatile array of supramolecular materials. Its shortcomings, however, include the uncontrolled hierarchical assembly into microtubes of heterogeneous size distribution and well-known cytotoxicity. This study rationalized heterochirality as a successful strategy to address both of these pitfalls and it provided an unprotected heterochiral dipeptide that self-organized into a homogeneous and optically clear hydrogel with excellent ability to sustain fibroblast cell proliferation and viability. Substitution of one l -amino acid with its d -enantiomer preserved the ability of the dipeptide to self-organize into nanotubes, as shown by single-crystal XRD analysis, whereby the pattern of electrostatic and hydrogen bonding interactions of the backbone was unaltered. The effect of heterochirality was manifested in subtle changes in the positioning of the aromatic side chains, which resulted in weaker intermolecular interactions between nanotubes. As a result, d -Phe- l -Phe self-organized into homogeneous nanofibrils with a diameter of 4 nm, corresponding to two layers of peptides around a water channel, and yielded a transparent hydrogel. In contrast with homochiral Phe-Phe stereoisomer, it formed stable hydrogels thermoreversibly. d -Phe- l -Phe displayed no amyloid toxicity in cell cultures with fibroblast cells proliferating in high numbers and viability on this biomaterial, marking it as a preferred substrate over tissue-culture plastic. Halogenation also enabled the tailoring of d -Phe- l -Phe self-organization. Fluorination allowed analogous supramolecular packing as confirmed by XRD, thus nanotube formation, and gave intermediate levels of bundling. In contrast, iodination was the most effective strategy to augment the stability of the resulting hydrogel, although at the expense of optical transparency and biocompatibility. Interestingly, iodine presence hindered the supramolecular packing into nanotubes, resulting instead into amphipathic layers of stacked peptides without the occurrence of halogen bonding. By unravelling fine details to control these materials at the meso- and macro-scale, this study significantly advanced our understanding of these systems.

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confidence: 99%

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

et al. 2020

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“…The sequence of the Nap-GFFY peptide was deemed necessary as a study substituting and/or changing the position of the amino acids concluded that both the position of each amino acid and the number of aromatic amino acids were deemed necessary in determining the potency of the adjuvant. [130,131] The absence of any amino acid in the Nap-GFFY hydrogel sequence was shown to cause a 10x reduction in the antibody titer after OVA vaccination in C57BL/6 mice, highlighting the importance of choosing specific amino acids in peptide bioconjugates that form hydrogels. It was found that if the phenylalanine amino acids were substituted with Gly, the compounds did not self-assemble, showing the importance of the aromatic amino acids in hydrogel formation.…”

Section: Hydrogel Propertiesmentioning

confidence: 99%

Peptide Hydrogels as Immunomaterials and Their Use in Cancer Immunotherapy Delivery

Falcone,

Ermis,

Tamay

et al. 2023

Adv Healthcare Materials

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Peptide‐based hydrogel biomaterials have emerged as an excellent strategy for immune system modulation. Peptide‐based hydrogels are supramolecular materials that self‐assemble into various nanostructures through various interactive forces (i.e., hydrogen bonding and hydrophobic interactions) and respond to microenvironmental stimuli (i.e., pH, temperature). While they have been reported in numerous biomedical applications, they have recently been deemed promising candidates to improve the efficacy of cancer immunotherapies and treatments. Immunotherapies seek to harness the body's immune system to preemptively protect against and treat various diseases, such as cancer. However, their low efficacy rates result in limited patient responses to treatment. Here, the immunomaterial's potential to improve these efficacy rates by either functioning as immune stimulators through direct immune system interactions and/or delivering a range of immune agents is highlighted. The chemical and physical properties of these peptide‐based materials that lead to immuno modulation and how one may design a system to achieve desired immune responses in a controllable manner are discussed. Works in the literature that reports peptide hydrogels as adjuvant systems and for the delivery of immunotherapies are highlighted. Finally, the future trends and possible developments based on peptide hydrogels for cancer immunotherapy applications are discussed.

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“…Based on the pure chiral hydrogel Nap-GFFY ( l -gel) containing three transformable chiral amino acid sites, Li et al 82 replaced l -amino acids with d -amino acids and obtained three heterarchical hydrogels, Nap-G D FFY (gel-1), Nap-GF D FY (gel-2), and Nap-GFF D Y (gel-3). The four kinds of hydrogels have differences in their gelation temperatures and the minimum gelation concentration.…”

Section: Factors Influencing the Formation Of Peptide Hydrogelsmentioning

confidence: 99%

Mechanisms and influencing factors of peptide hydrogel formation and biomedicine applications of hydrogels

Zhang,

Zhao,

2023

Soft Matter

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The substitution of a single amino acid with its enantiomer for control over the adjuvant activity of self-assembling peptides

Abstract: The substitution of a single amino acid with its enantiomer in Nap-GFFY conferred different self-assembly performances and distinct adjuvant activities on the corresponding peptides.

Cited by 7 publications

References 39 publications

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

Heterochirality and Halogenation Control Phe-Phe Hierarchical Assembly

Peptide Hydrogels as Immunomaterials and Their Use in Cancer Immunotherapy Delivery

Mechanisms and influencing factors of peptide hydrogel formation and biomedicine applications of hydrogels

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