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Titolo:
Differential activities of decapeptide agonists of human C5a: the conformational effects of backbone N-methylation
Autore:
Vogen, SM; Paczkowski, NJ; Kirnarsky, L; Short, A; Whitmore, JB; Sherman, SA; Taylor, SM; Sanderson, SD;
Indirizzi:
Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, Omaha, NE 68198USA Univ Nebraska Omaha NE USA 68198 es Canc & Allied Dis, Omaha, NE 68198USA Univ Queensland, Dept Physiol & Pharmacol, St Lucia, Qld 4072, Australia Univ Queensland St Lucia Qld Australia 4072 St Lucia, Qld 4072, Australia
Titolo Testata:
INTERNATIONAL IMMUNOPHARMACOLOGY
fascicolo: 12, volume: 1, anno: 2001,
pagine: 2151 - 2162
SICI:
1567-5769(200111)1:12<2151:DAODAO>2.0.ZU;2-2
Fonte:
ISI
Lingua:
ENG
Soggetto:
RECEPTOR-BINDING; UMBILICAL ARTERY; ANAPHYLATOXIN;
Keywords:
N-methylation; response-selective C5a agonists;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Sanderson, SD Univ Nebraska, Med Ctr, Eppley Inst Res Canc & Allied Dis, 986805 Med Ctr,600 So 52nd St, Omaha, NE 68198 USA Univ Nebraska 986805 Med Ctr,600 So 52nd St Omaha NE USA 68198
Citazione:
S.M. Vogen et al., "Differential activities of decapeptide agonists of human C5a: the conformational effects of backbone N-methylation", INT IMMUNO, 1(12), 2001, pp. 2151-2162

Abstract

Analogues of the potent, conformationally biased, decapeptide agonist of human C5a anaphylatoxin, C5a(65-74)Y65,F67,P69,P71,D-Ala73 (YSFKPMPLaR, peptide 54), were synthesized with methyl groups occupying specific C5a,, amidenitrogen atoms along the peptide backbone. This N-methylation induced crucial extended backbone conformations in a manner similar to the two Pro residues, but without eliminating the contributions made by the side-chain of the residue for which Pro was substituted. The presence of backbone N-methylgroups on peptide 54 analogues had pronounced detrimental effects on the ability to bind and activate C5aRs expressed on human PMNs, but not on the ability to contract smooth muscle of human umbilical artery. Several N-methylated analogues of peptide 54 (peptides 56, 67, 124, 125, and 137) were significantly more selective for smooth muscle contraction, which is mediated by tissue resident macrophages, than for enzyme release from PMNs. Indeed, peptide 67, YSFKDMP(MeL)aR was almost 3000-fold more selective for smooth muscle contraction than for PMN enzyme release. Consistent with these differential activities was the observation that peptide 67 expressed a significantly greater binding affinity to C5aRs expressed on rat macrophages than onrat PMNs. This differential activity was also observed in vivo in the rat where peptide 67 induced a hypotensive response similar to peptide 54 and rhuC5a, but without accompanying neutropenia. (C) 2001 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 18/01/20 alle ore 01:51:14