Bicyclic peptides as type I/type II beta-turn scaffolds.
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.
Lombardi
A
A
Centro Interdipartimentale di Ricerca sui Peptidi Bioattivi CEINGE--Biotecnologie Avanzate, Napoli, Italy.
D'Auria
G
G
Saviano
M
M
Maglio
O
O
Nastri
F
F
Quartara
L
L
Pedone
C
C
Pavone
V
V
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
D010456:Peptides, Cyclic; C090951:MEN 10627; D015288:Neurokinin A