NEW ACTIVE ANALOGS OF CUCURBITA-MAXIMA TRYPSIN-INHIBITOR-III (CMTI-III) MODIFIED IN THE NONCONTACT REGION

Four new analogues of trypsin inhibitor CMTI-III(3 - 28) = [desArg(1), desVal(2),desGly(29)]CMTI-III which was recently shown to be fully act ive, were synthesized by the solid-phase method. The introduction of g lycine in position 9 (peptide 1) and Gly-Pro-Gly (peptide 2) and Gly-P ro-Asn (peptide 3) in the regions 17-19 and 23-25, respectively, did n ot change the antitrypsin activity of all modified peptides. All of th ese substitutions are presumed to be outside the trypsin-binding loop as judged from the X-ray structure of the complex between beta-trypsin and the related inhibitor CMTI-I. Also the fourth analogue which was substituted in all the positions mentioned, exhibited the full activit y.