Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
New conformationally homogeneous beta-turn antagonists of the human B-2 kinin receptor
Autore:
Monteagudo, ES; Calvani, F; Catrambone, F; Fincham, CI; Madami, A; Meini, S; Terracciano, R;
Indirizzi:
Menarini Ricerche SpA, Dept Chem, I-00040 Pomezia, Italy Menarini RicercheSpA Pomezia Italy I-00040 Chem, I-00040 Pomezia, Italy Menarini Ricerche SpA, Dept Drug Design, I-00040 Pomezia, Italy Menarini Ricerche SpA Pomezia Italy I-00040 sign, I-00040 Pomezia, Italy Menarini Ricerche SpA, Dept Pharmacol, I-00040 Pomezia, Italy Menarini Ricerche SpA Pomezia Italy I-00040 acol, I-00040 Pomezia, Italy
Titolo Testata:
JOURNAL OF PEPTIDE SCIENCE
fascicolo: 5, volume: 7, anno: 2001,
pagine: 270 - 283
SICI:
1075-2617(200105)7:5<270:NCHBAO>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRADYKININ RECEPTOR; CYCLIC PENTAPEPTIDES; MOLECULAR-DYNAMICS; MET-ENKEPHALIN; HIGH-AFFINITY; AMINO-ACIDS; PEPTIDES; POTENT; NMR; EXPRESSION;
Keywords:
antagonists; biological activity; bradykinin; conformation; cyclic peptides; NMR studies; synthesis;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
38
Recensione:
Indirizzi per estratti:
Indirizzo: Monteagudo, ES Menarini Ricerche SpA, Dept Chem, Via tito Speri 10, I-00040 Pomezia, Italy Menarini Ricerche SpA Via tito Speri 10 Pomezia Italy I-00040
Citazione:
E.S. Monteagudo et al., "New conformationally homogeneous beta-turn antagonists of the human B-2 kinin receptor", J PEPT SCI, 7(5), 2001, pp. 270-283

Abstract

We have designed and synthesized a conformationally homogeneous series of cyclic pentapeptides of the general structure c[Pro-aa(i)-D-Tic-Oic-aa(i+3)] which adopt a type-II beta -turn conformation believed important for highaffinity antagonism of the bradykinin (BK) beta (2) receptor. We incorporated D-Tic and octahydroindole-2-carboxylic acid (Oic) residues (present in known active antagonists) in a cyclic pentapeptide that would place the D-aa in the i + 1 position of the beta -turn and a proline as a bridge betweenthe C- and N-termini sides of the turn. In positions i and i + 3 alkyl, aromatic, polar or charged amino acids could be introduced without dramatically changing the overall structure. Ten analogues were studied using H-1 nuclear magnetic resonance (NMR) and evaluated for their binding affinity for the human R, receptor. The NMR data in dimethylsulfoxide (DMSO) confirmed the structural homogeneity within. We class and, on the basis of this, one representative member of the series was chosen for a detailed structure determination using NMR data in sodium dodecylsulphate (SDS) micelles and molecular dynamics calculations. Despite the structural similarity, the binding affinity of the ten analogues was strongly influenced by the nature of the side-chains in positions i and i + 3, with the doubly charged analogue 49 (pK(i) = 6.2) proving best. This compound may serve as the starting point for the discovery of new non-peptide bradykinin beta (2) receptor antagonists. Copyright (C) 2001 European Peptide Society and John Wiley & Sons. Ltd.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 16:48:27