A CONFORMATIONAL STUDY IN SOLUTION OF PRO-SOMATOSTATIN FRAGMENTS BY NMR AND COMPUTATIONAL METHODS

The results of a conformational study by nuclear magnetic spectroscopy and computational methods on a series of point-mutated synthetic pept ides, containing 14 amino acid residues and mimicking the region conta ining the Arg-Lys dibasic cleavage site of pro-somatostatin, have conf irmed the possible role of a well defined secondary structure in the r ecognition phenomenon by processing enzymes. The importance of the res idues located near the Arg-Lys dibasic site in the C-terminal region o f the pro-hormone for the cleavage of the precursor into somatostatin- 14 has been confirmed. The present structural analysis indicates the o ccurrence of two beta-turns in the 4-7 and 11-14 regions, flanking the cleavage site, for all the peptides recognized as substrates by the p rocessing enzyme. Interestingly, in the point-mutated. analogue not pr ocessed by the enzyme and containing the replacement of proline by ala nine in position 5 the first beta-turn is displaced by one residue and involves the Ala(5)-Arg(8) segment. This observation may explain the lack of recognition by the maturation enzyme, (C) 1998 European Peptid e Society and John Wiley & Sons, Ltd.