DISTANCE BETWEEN THE BASIC GROUP OF THE AMINO-ACID-RESIDUES SIDE-CHAIN IN POSITION P-1 OF TRYPSIN-INHIBITOR CMTI-III AND ASP(189) IN THE SUBSTRATE POCKET OF TRYPSIN HAS AN ESSENTIAL INFLUENCE ON THE INHIBITORYACTIVITY

Three new analogues of trypsin inhibitor CMTI-III were synthesized by the solid-phase method: [Lys(5)]-CMTI-III, Orn(5)]CMTI-III and [Dab(5) ]CMTI-III. Only one analogue with L-lysine residue in position P-1 sho wed inhibitory activity of the same order of magnitude as did wild CMT I-III. Two remaining analogues were completely inactive. A conclusion was drawn that the distance between the basic group of the amino acid residue's side chain in position P-1 of the trypsin inhibitor CMTI-III and Asp(189) in the substrate pocket of trypsin plays an essential ro le for the trypsin-inhibitor interaction. (C) 1997 Academic Press.