A synthetic 13-residue peptide designed to resemble the primary binding site of the basic pancreatic trypsin inhibitor.
A peptide, AC-Pro-Cys-Lys-Ala-Arg-Ile-DPhe-Pro-Tyr-Gly-Gly-Cys-Arg-NH2, which resembles the binding site of the basic pancreatic trypsin inhibitor, has been prepared by solid-phase peptide synthesis. A partially protected peptide was first obtained from the solid-phase product by removal of all side-chain protecting groups except the acetamidomethyl (Acm) groups on the cysteines. This di-Acm-peptide was deprotected, with concomitant formation of the cyclic product, by treatment with I2 in AcOH. The cyclic 13-residue peptide is a reversible, competitive inhibitor of trypsin with a Ki (app) of 2 . 10(-6) M, but loses its inhibitory activity upon incubation with trypsin. The di-Acm-peptide precursor has a Ki (app) of 5 . 10(-5) M and is deactivated more rapidly by trypsin. The effectiveness of the 13-residue peptides as inhibitors is in part attributed to the conformation induced by the beta-turn directing the -DPhe-Pro portion of the sequence.
D000595:Amino Acid Sequence; D007611:Aprotinin / Q000138:chemical synthesis*; D001665:Binding Sites; D004355:Drug Stability; D006207:Half-Life; D007700:Kinetics; D008722:Methods; D010455:Peptides / Q000138:chemical synthesis; D011487:Protein Conformation; D014357:Trypsin / Q000378:metabolism
D010455:Peptides; D007611:Aprotinin; D014357:Trypsin