Physicochemical behavior of polylysine-[HAV-VPS peptide] constructs at theair-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 catio nic and amphoteric polymeric polypeptides. In the present paper, we describ e the physicochemical characterization of three branched polypeptide-[HAV-V P3(110-121) peptide] constructs, where the peptide is attached to the polym er side chains by disulfide linkage. The surface activity of these three co njugates has been studied as a function of time and concentration in the su bphase. Moreover, its insertion into phospholipid DPP C ( dipalmitoylphosph atidylcholine) monolayers has also been determine d. The results show that these constructs are surface active and can insert into the lipid monolayer s. AK construct is slightly more active than EAK and SAK constructs both in the presence and absence of DPPC monolayers. This behavior suggests that c onstruct disposition at interfaces is mainly dependent on nonsubstituted si de chains. Fluorescence polarization studies, performed with DPPC vesicles saturated with either DPH (1,6-diphenyl-1,3,5-hexatriene;) or ANS (1-anilin o-8-naphthalenesulfonic acid), indicate a strong rigidifying effect of the three constructs on the polar heads and alkyl chains of bilayers.