SELECTION OF PEPTIDE INHIBITORS OF INTERACTIONS INVOLVED IN COMPLEX PROTEIN ASSEMBLIES - ASSOCIATION OF THE CORE AND SURFACE-ANTIGENS OF HEPATITIS-B VIRUS

As an example for studies of contacts involved in complex biological s ystems, peptide ligands that bind to the core antigen of hepatitis B v irus (HBcAg) have been selected from a random hexapeptide library disp layed on filamentous phage. Affinity-purified phage bearing aa seqnenc e LLGRMK, or some related sequences, bound full-length or truncated HB cAg but did not bind denatured HBcAg. The long (L), but not the short (S), hepatitis B virus envelope polypeptide, when synthesized in an in vitro system, bound firmly to HBcAg, indicating that interaction betw een HBcAg and the pre-S region of the L polypeptide is critical for vi rus morphogenesis. This interaction was inhibited by peptide ALLGRMKG, suggesting that this and related small molecules may inhibit viral as sembly.