CHEMICAL SYNTHESIS AND KINETIC STUDIES OF DIMERIC ANALOGUES OF TRYPSIN INHIBITOR SFTI-1 AND ITS TWO ANALOGUES CONTAINING A CARBONYL BRIDGE

摘要

SFTI-1 (Gly-Arg-Cys-Thr-Lys~5-Ser~6-Ile-Pro-Pro-Cys-Phe-Pro-Asp, disulfide bridge and head to tail cyclization) is the smallest and the most potent peptidic trypsin inhibitor known so far. For this reason it became an attractive object for studying enzyme-inhibitor interaction. SFTI-1 displays high sequential and structural homology with the binding loop of the family of Bowman-Birk inhibitors (BBIs). Lys~5-Ser~6 is the inhibitor reactive site (Pi-Pi'). Here we report the chemical synthesis and kinetic studies of a series of SFTI-1 analogues based on double sequence of the wild inhibitor. The question, whether such dimeric analogues can combine features from both, BBI and SFTI-1, such as the ability of the BBIs to allow dual inhibition, and the small size and constrained nature of SFTI-1, has been asked here.