title: A type-II beta-turn, proline-containing, cyclic pentapeptide as a building block for the construction of models of the cleavage site of pro-oxytocin.
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 beta-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 beta-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-lI beta-turn, has been synthesized. The presence of a type-II beta-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.
authors.affiliation: Department of Chemical Process Engineering, University of Padova, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Dettin
authors.forename: L
authors.initials: L
authors.lastname: Falcigno
authors.forename: T
authors.initials: T
authors.lastname: Campanile
authors.forename: C
authors.initials: C
authors.lastname: Scarinci
authors.forename: G
authors.initials: G
authors.lastname: D'Auria
authors.forename: M
authors.initials: M
authors.lastname: Cusin
authors.forename: L
authors.initials: L
authors.lastname: Paolillo
authors.forename: C
authors.initials: C
authors.lastname: Di Bello
mesh_terms: D016282:Aspartic Acid Endopeptidases / Q000737:chemistry; D002942:Circular Dichroism; D006868:Hydrolysis; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008956:Models, Chemical; D008968:Molecular Conformation; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010121:Oxytocin / Q000031:analogs & derivatives* / Q000737:chemistry*; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011392:Proline / Q000737:chemistry; D043484:Proprotein Convertases; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
chemical_list: D009842:Oligopeptides; D010456:Peptides, Cyclic; D010121:Oxytocin; C046278:oxytocin, Gly-Lys-Arg-; D011392:Proline; D043484:Proprotein Convertases; D016282:Aspartic Acid Endopeptidases