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

A family of four self‐assembling lipopeptides containing Ala‐Lys peptides attached to a C 16 aliphatic chain were synthesised. These compounds form two enantiomeric pairs that bear a diastereomeric relationship to one another (C 16 ‐ l ‐Ala‐ l ‐Lys/C 16 ‐ d ‐Ala‐ d ‐Lys) and (C 16 ‐ d ‐Ala‐ l ‐Lys/C 16 ‐ 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.