Effect of phospholipid bilayers on solution conformation of branched polymeric polypeptides and peptide-polymer conjugates

This report provides a detailed analysis on the influence of phosholipid bi layers on the conformation of poly[Lys(X-i-DL-Ala(m))] (XAK, where X = Ser, Orn, Glu, or AcGlu) type branched polypeptides and their peptide conjugate s. CD spectra of polycationic (SAK, OAK), amphoteric (EAK), or polyanionic (Ac-EAK) polylysine derivatives were recorded in 0.25M acetate buffer at pH 7.4 as well as in the presence of DPPC or DPPC/PG (95/5, 80/20 mol/mol) li posomes. Based on these data, two groups of polypeptides are described. Gro up one contains polypeptides with significantly ordered conformation even i n buffer solution (SAK, AcEAK), which is essentially not altered by phospho lipids. Group two, branched polypeptides (OAK, EAK), with only partially or dered conformation in aqueous solution in the presence of phospholipid bila yers with high PG content, could adopt more (EAK) or less (OAK) ordered alp ha -helical structure depending on their charge properties. In addition, we report on the synthesis of two new sets of oligopeptide-branched polypepti de conjugates. Studies with selected conjugates suggest that these compound s are highly ordered in buffer solution almost regardless from the helix-fo rming ability of the carrier (AK, SAK, EAK) and from the hydrophilic/hydrop hobic character of peptides attached (AVKDEL vs FWRGDLVFDFQV). Addition of phospholipid bilayers with different composition essentially had no modifyi ng effect on conformation of conjugates. From this we can conclude that the convalently coupled oligopeptides has a predominant effect of the conforma tional properties of conjugates. (C) 2001 John Wiley & Sons, Inc.