Selection of peptide inhibitors of interactions involved in complex protein assemblies: association of the core and surface antigens of hepatitis B virus.

• DOI: 10.1073/pnas.92.6.2194
• Publication Date: 2006-05-31T13:29:22Z
• Authors: M R Dyson; K Murray
• Keywords: Hepatitis B virus; 0303 health sciences; Hepatitis B Surface Antigens; Base Sequence; Transcription, Genetic; Molecular Sequence Data; Ligands; Hepatitis B Core Antigens; Polymerase Chain Reaction; Protein Structure, Secondary; Recombinant Proteins; 3. Good health; Random Allocation; 03 medical and health sciences; Viral Envelope Proteins; Protein Biosynthesis; Mutagenesis, Site-Directed; Point Mutation; Bacteriophages; Amino Acid Sequence; Oligopeptides; DNA Primers

As an example for studies of contacts involved in complex biological systems, peptide ligands that bind to the core antigen of hepatitis B virus (HBcAg) have been selected from a random hexapeptide library displayed on filamentous phage. Affinity-purified phage bearing aa sequence LLGRMK, or some related sequences, bound full-length or truncated HBcAg 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 between HBcAg and the pre-S region of the L polypeptide is critical for virus morphogenesis. This interaction was inhibited by peptide ALLGRMKG, suggesting that this and related small molecules may inhibit viral assembly.