A type-II β-turn, proline-containing, cyclic pentapeptide as a building block for the construction of models of the cleavage site of pro-oxytocin

✍ Scribed by Monica Dettin; Lucia Falcigno; Tiziano Campanile; Claudia Scarinci; Gabriella D'Auria; Marina Cusin; Livio Paolillo; Carlo Di Bello

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 406 KB
• Volume: 7
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.330

✦ Synopsis

Abstract

Previous studies have indicated that proteolytic activation of pro‐hormones and pro‐proteins occurs most frequently at the level of basic amino acids arranged in doublets and that the dibasic sites are situated in or next to β‐turns. Investigations utilizing synthetic peptides reproducing the N‐terminal processing domain of pro‐oxytocin‐neurophysin have suggested a close relationship between the secondary structure of the cleavage locus and enzyme recognition, the minimal recognized sequence being the ‐Pro‐Leu‐Gly‐Gly‐Lys‐Arg‐Ala‐Val‐Leu‐ segment of the native precursor. NMR investigations and energy minimization studies have demonstrated that this sequence is organized in two type‐II β‐turns involving the ‐Pro‐Leu‐Gly‐Gly‐ and ‐Lys‐Arg‐Ala‐Val‐ sequences. To further strengthen the above reported hypothesis and to study the role of turn subtypes, a new proline containing cyclic substrate of the processing enzyme, in which the N‐terminal side that comes before the Lys‐Arg pair is constrained to adopt a type‐II β‐turn, has been synthesized. The presence of a type‐II β‐turn structure in this cyclic peptide model has been demonstrated by a combined NMR, CD and FT‐IR absorption investigation. A preliminary study shows that PC1 is able to recognize and process our constrained substrate. Copyright © 2001 European Peptide Society and John Wiley & Sons, Ltd.