Self-Assembly and Antimicrobial Activity of Lipopeptides Containing Lysine-Rich Tripeptides
Anindyasundar Adak, Valeria Castelletto, Ana de Sousa, Kimon Andreas G. Karatzas, C. Wilkinson, Nikul Khunti, Jani Seitsonen, Ian W. Hamley
Abstract
High Resolution Image Download MS PowerPoint Slide 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 C 16 -YKK or C 16 -WKK (with two l -lysine residues) or their respective derivatives containing d -lysine (k), i.e., C 16 -Ykk and C 16 -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.