Enantiomeric and Diastereomeric Self‐Assembled Multivalent Nanostructures: Understanding the Effects of Chirality on Binding to Polyanionic Heparin and DNA

Abstract

AbstractA family of four self‐assembling lipopeptides containing Ala‐Lys peptides attached to a C16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C16‐l‐Ala‐l‐Lys/C16‐d‐Ala‐d‐Lys) and (C16‐d‐Ala‐l‐Lys/C16‐l‐Ala‐d‐Lys). These diastereomeric pairs have very different critical micelle concentrations (CMCs). The self‐assembled multivalent (SAMul) systems bind biological polyanions as a result of the cationic lysine groups on their surfaces. For heparin binding, there was no significant enantioselectivity, but there was a binding preference for the diastereomeric assemblies with lower CMCs. Conversely, for DNA binding, there was significant enantioselectivity for systems displaying d‐lysine ligands, with a further slight preference for attachment to l‐alanine, with the CMC being irrelevant.