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

Proc Natl Acad Sci U S A. 1995 Mar 14;92(6):2194-8. doi: 10.1073/pnas.92.6.2194.

Abstract

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Bacteriophages / metabolism*
  • Base Sequence
  • DNA Primers
  • Hepatitis B Core Antigens / biosynthesis
  • Hepatitis B Core Antigens / chemistry
  • Hepatitis B Core Antigens / metabolism*
  • Hepatitis B Surface Antigens / biosynthesis
  • Hepatitis B Surface Antigens / chemistry
  • Hepatitis B Surface Antigens / metabolism*
  • Hepatitis B virus / metabolism*
  • Ligands
  • Molecular Sequence Data
  • Mutagenesis, Site-Directed
  • Oligopeptides / chemistry
  • Oligopeptides / metabolism*
  • Point Mutation
  • Polymerase Chain Reaction
  • Protein Biosynthesis
  • Protein Structure, Secondary
  • Random Allocation
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / metabolism
  • Transcription, Genetic
  • Viral Envelope Proteins / metabolism*

Substances

  • DNA Primers
  • Hepatitis B Core Antigens
  • Hepatitis B Surface Antigens
  • Ligands
  • Oligopeptides
  • Recombinant Proteins
  • Viral Envelope Proteins