Studies on the synthesis of proteinase inhibitors. I. Synthesis and activity of nonapeptide fragments of soybean Bowman-Birk inhibitor.
Two heterodetic cyclic nonapeptides, X-Cys-Thr-Lys-Ser-Asn-Pro-Pro-Gln-Cys-Y (Ia: X = Ac,  Y = NH2; Ib: X = H, Y = OH), which correspond to residues 14-22 in the sequence of Bowman-Birk inhibitor, have been synthesized by Merrifield's solid-phase method. Inhibitory activities of Ia and Ib on tryptic hydrolysis of amide and ester substrates were examined. When Gly2-Lys-Gly3 and Tos-Arg-OMe were used as substrates, the values of I50 for the peptide Ia were calculated to  be 3.6 micron and 40 micron, respectively. When Gly2-Lys-Gly3 was used as a substrate, the value of Ki was calculated to be 1.5 micron. Ia was hydrolyzed slowly by trypsin, losing the inhibitory activity. When the Lys-Ser bond of Ia  was cleved with trypsin, the modified Ia could not be regenerated by trypsin. The linear peptide S, S'-dicarboxamidomethyl-Ia also was inactive and appeared to be a good substrate. Optical rotatory dispersion studies showed that the active fragments have characteristic  conformations  which  were lost upon modification to inactive derivatives.
D002850:Chromatography, Gel; D007700:Kinetics; D008722:Methods; D010455:Peptides / Q000138:chemical synthesis / Q000494:pharmacology; D014358:Trypsin Inhibitor, Bowman-Birk Soybean / Q000138:chemical synthesis* / Q000494:pharmacology; D014361:Trypsin Inhibitors / Q000138:chemical synthesis*
D010455:Peptides; D014358:Trypsin Inhibitor, Bowman-Birk Soybean; D014361:Trypsin Inhibitors