Physicochemical behavior of polylysine-[HAV-VP3 peptide] constructs at the air-water interface

Branched-chain polypeptides based on a polylysine backbone were synthesized for use as delivery systems for biologically active molecules. To develop a new immunoadjuvant system for hepatitis A virus (HAV) antigens, a peptide fragment (110-121) of the VP3 hepatitis A protein has been linked to cationic and amphoteric polymeric polypeptides. In the present paper, we describe the physicochemical characterization of three branched polypeptide-[HAV-VP3(110-121) peptide] constructs, where the peptide is attached to the polymer side chains by disulfide linkage. The surface activity of these three conjugates has been studied as a function of time and concentration in the subphase. Moreover, its insertion into phospholipid DPPC (dipalmitoylphosphatidylcholine) monolayers has also been determined. The results show that these constructs are surface active and can insert into the lipid monolayers. AK construct is slightly more active than EAK and SAK constructs both in the presence and absence of DPPC monolayers. This behavior suggests that construct disposition at interfaces is mainly dependent on nonsubstituted side chains. Fluorescence polarization studies, performed with DPPC vesicles saturated with either DPH (1,6-diphenyl-1,3,5-hexatriene) or ANS (1-anilino-8-naphthalenesulfonic acid), indicate a strong rigidifying effect of the three constructs on the polar heads and alkyl chains of bilayers.