Chirality and pH influence the self-assembly of antimicrobial Lipopeptides with diverse nanostructures

Adak, A., Castelletto, V. ORCID: https://orcid.org/0000-0002-3705-0162, Mendes, B., Barrett, G. ORCID: https://orcid.org/0000-0003-1509-0179, Seitsonen, J. and Hamley, I. W. ORCID: https://orcid.org/0000-0002-4549-0926 (2024) Chirality and pH influence the self-assembly of antimicrobial Lipopeptides with diverse nanostructures. ACS Applied Bio Materials. ISSN 2576-6422 doi: 10.1021/acsabm.4c00664

Abstract/Summary

Chirality plays a crucial role in the self-assembly of biomolecules in nature. Peptides show chirality-dependent conformation and self-assembly. Lipidation of peptides occurs in vivo and has recently been exploited in designed conjugates to drive self-assembly and enhance bioactivity. Here, a library of pH-responsive homochiral and heterochiral lipidated tripeptides has been designed. The designed lipopeptides comprise homochiral C16–YKK or C16–WKK (where all the amino acids are l-isomers), and two heterochiral conjugates C16–Ykk and C16–Wkk (where the two lysines are d-isomers). The self-assembly of all the synthesized lipopeptides in aqueous solution was examined using a combination of spectroscopic methods along with cryogenic-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). Interestingly, it was observed that at acidic pH all the lipopeptides self-assemble into micelles, whereas at basic pH the homochiral lipopeptides self-assemble into nanofibers, whereas the heterochiral lipopeptides self-assemble into nanotapes and nanotubes. A pH switch was demonstrated using a thioflavin T fluorescence probe of β-sheet structure present in the extended structures at pH 8. We demonstrate that both chirality and pH in lipopeptides influence the self-assembly behavior of the model tripeptides, which also show promising bioactivity. Good cytocompatibility is observed in hemolytic assays and antimicrobial activity against both Gram-negative and Gram-positive bacteria is shown through the determination of minimum inhibition concentration (MIC) and minimum bactericidal concentration (MBC) values and live/dead bacteria staining assay.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/117448
Item Type	Article
Refereed	Yes
Divisions	Interdisciplinary centres and themes > Chemical Analysis Facility (CAF) Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher	American Chemical Society (ACS)
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