title: Bicyclic peptides as type I/type II beta-turn scaffolds.
abstract: We recently reported the rational design, synthetics, and structural characterization of the most potent and selective peptide-based neurokinin A antagonist thus far described: cyclo(Met1-Asp2-Trp3-Phe4-Dap5-Leu6)cyclo(2 beta-5 beta). Its bicyclic structure is characterized by a type I and a type II two beta-turn around Trp3-Phe4 and Leu6-Met1, respectively. In order to understand whether the two different beta-turned structures are determined by the bicyclic structure or by the amino acid type at the corner positions, we have synthesized the pseudo-symmetrical analogue cyclo(Phe1-Asp2-Trp3-Phe4-Dap5-Trp6)cyclo(2 beta-5 beta). The structural characterization in the crystal state and in solution, here reported, gives an experimental evidence that the backbone of the bicyclic structure is a rigid scaffold that can be used to build both a type I and type II beta-turn independently from the amino acid composition.
authors.affiliation: Centro Interdipartimentale di Ricerca sui Peptidi Bioattivi CEINGE--Biotecnologie Avanzate, Napoli, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Lombardi
authors.forename: G
authors.initials: G
authors.lastname: D'Auria
authors.forename: M
authors.initials: M
authors.lastname: Saviano
authors.forename: O
authors.initials: O
authors.lastname: Maglio
authors.forename: F
authors.initials: F
authors.lastname: Nastri
authors.forename: L
authors.initials: L
authors.lastname: Quartara
authors.forename: C
authors.initials: C
authors.lastname: Pedone
authors.forename: V
authors.initials: V
authors.lastname: Pavone
mesh_terms: D018360:Crystallography, X-Ray; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015288:Neurokinin A / Q000037:antagonists & inhibitors; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011487:Protein Conformation; D017433:Protein Structure, Secondary
chemical_list: D010456:Peptides, Cyclic; C090951:MEN 10627; D015288:Neurokinin A