Self-assembly and antimicrobial activity of lipopeptides containing lysine-rich tripeptides

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Adak, A., Castelletto, V. orcid id iconORCID: https://orcid.org/0000-0002-3705-0162, de Sousa, A., Karatzas, K.-A., Wilkinson, C., Khunti, N., Seitsonen, J. and Hamley, I. W. orcid id iconORCID: https://orcid.org/0000-0002-4549-0926 (2024) Self-assembly and antimicrobial activity of lipopeptides containing lysine-rich tripeptides. Biomacromolecules. ISSN 1525-7797 doi: 10.1021/acs.biomac.3c01184

Abstract/Summary

The conformation and self-assembly of two pairs of model lipidated tripeptides in aqueous solution are probed using a combination of spectroscopic methods along with cryogenic-transmission electron microscopy (cryo-TEM) and small-angle X-ray scattering (SAXS). The palmitoylated lipopeptides comprise C16-YKK or C16-WKK (with two l-lysine residues) or their respective derivatives containing d-lysine (k), i.e., C16-Ykk and C16-Wkk. All four molecules self-assemble into spherical micelles which show structure factor effects in SAXS profiles due to intermicellar packing in aqueous solution. Consistent with micellar structures, the tripeptides in the coronas have a largely unordered conformation, as probed using spectroscopic methods. The molecules are found to have good cytocompatibility with fibroblasts at sufficiently low concentrations, although some loss of cell viability is noted at the highest concentrations examined (above the critical aggregation concentration of the lipopeptides, determined from fluorescence dye probe measurements). Preliminary tests also showed antimicrobial activity against both Gram-negative and Gram-positive bacteria.

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Item Type Article
URI https://reading-clone.eprints-hosting.org/id/eprint/114674
Identification Number/DOI 10.1021/acs.biomac.3c01184
Refereed Yes
Divisions Interdisciplinary centres and themes > Chemical Analysis Facility (CAF)
Life Sciences > School of Chemistry, Food and Pharmacy > Department of Chemistry
Publisher ACS
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