Synthetic peptide mimics of the Bowman-Birk inhibitor protein.
Proteins of the Bowman-Birk inhibitor family of serine proteinase inhibitors interact with the enzymes they inhibit via an exposed surface loop that adopts the canonical proteinase inhibitory conformation. The resulting non-covalent complex renders the proteinase inactive. This inhibition mechanism is common for the majority of serine proteinase inhibitor proteins and many analogous examples are known. A particular feature of the Bowman-Birk inhibitor protein, however, is that the interacting loop is a particularly well-defined disulfide-linked short beta-sheet region. Moreover, synthetic peptides based on this region keep the same structure as the corresponding part of the full sized protein and also retain inhibitory activity. This review describes the background to inhibition by Bowman-Birk inhibitor proteins (and derived peptides) and shows how peptides based on the reactive site can be manipulated in order to generate potent proteinase inhibitors with redirected specificities.
McBride
J D
JD
Department of Chemistry, Imperial College, London, South Kensington SW7 2AY, UK.
Leatherbarrow
R J
RJ
D000595:Amino Acid Sequence; D004355:Drug Stability; D006868:Hydrolysis; D008958:Models, Molecular; D018716:Molecular Mimicry; D008969:Molecular Sequence Data; D019151:Peptide Library; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry*; D011487:Protein Conformation; D015842:Serine Proteinase Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000737:chemistry* / Q000494:pharmacology
D019151:Peptide Library; D010456:Peptides, Cyclic; D015842:Serine Proteinase Inhibitors; D014358:Trypsin Inhibitor, Bowman-Birk Soybean