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 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.
Dyson
M R
MR
Institute of Cell and Molecular Biology, University of Edinburgh, Scotland.
Murray
K
K
D000595:Amino Acid Sequence; D001435:Bacteriophages / Q000378:metabolism*; D001483:Base Sequence; D017931:DNA Primers; D006512:Hepatitis B Core Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006514:Hepatitis B Surface Antigens / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D006515:Hepatitis B virus / Q000378:metabolism*; D008024:Ligands; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D009842:Oligopeptides / Q000737:chemistry / Q000378:metabolism*; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D017433:Protein Structure, Secondary; D011897:Random Allocation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014158:Transcription, Genetic; D014759:Viral Envelope Proteins / Q000378:metabolism*
D017931:DNA Primers; D006512:Hepatitis B Core Antigens; D006514:Hepatitis B Surface Antigens; D008024:Ligands; D009842:Oligopeptides; D011994:Recombinant Proteins; D014759:Viral Envelope Proteins