Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Structure-activity studies at the rat tachykinin NK2 receptor: effect of substitution at position 5 of neurokinin A
Autore:
Comis, A; Burcher, E;
Indirizzi:
Univ New S Wales, Sch Physiol & Pharmacol, Sydney, NSW 2052, Australia Univ New S Wales Sydney NSW Australia 2052 l, Sydney, NSW 2052, Australia
Titolo Testata:
JOURNAL OF PEPTIDE RESEARCH
fascicolo: 3, volume: 53, anno: 1999,
pagine: 337 - 342
SICI:
1397-002X(199903)53:3<337:SSATRT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
SELECTIVE AGONISTS; BINDING-SITES; AUTORADIOGRAPHIC LOCALIZATION; SUBSTANCE-P; ANTAGONISTS; DOMAINS; FUNDUS;
Keywords:
neurokinin; NK2 receptor; rat fundus; structure-activity; tachykinin;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
14
Recensione:
Indirizzi per estratti:
Indirizzo: Burcher, E Univ New S Wales, Sch Physiol & Pharmacol, Sydney, NSW 2052, Australia Univ New S Wales Sydney NSW Australia 2052 NSW 2052, Australia
Citazione:
A. Comis e E. Burcher, "Structure-activity studies at the rat tachykinin NK2 receptor: effect of substitution at position 5 of neurokinin A", J PEPT RES, 53(3), 1999, pp. 337-342

Abstract

A series of analogues of neurokinin A(4-10) was synthesized using solid phase techniques with Chiron pins, and purified by HPLC. The potencies of 10 peptides with substitution at Ser(5) were assessed at rat fundus NK2 receptors. In membrane binding studies with [I-125)-[Lys(5),Tyr(I-2)(7),MeLeu(9),Nle(10)]-NKA(4-10), all compounds except [Asp(5)]INKA(4-10) showed reasonable affinity, and analogues with Lys and Arg substitutions were fivefold more potent than NKA(4-10). In functional studies, all peptides were able to contract the rat isolated fundus strips. Analogues with Phe, His and Asn substitutions were substantially weaker in functional than in binding studies,whereas there was an excellent correlation (r = 0.95) between binding and functional potency for the remaining seven peptides.[Phe(5)]NKA(4-10) is in fact neurokinin B(4-10) and this residue may be critical in determining selectivity between NK2 and NK3 receptors. Analogues with a basic residue (Lys, Arg) at position 5 showed both increased affinity and functional potency, whereas the neutral [Asn(5)]NKA(4-10) was equallyas weak in contractile studies as the acidic [Asp(5)]NKA(4-10). However, [Glu(5)]NKA(4-10) and [Gln(5)]NKA(4-10) were no different from NKA(4-10). Our results could indicate the presence of a negative charge on the NK2 receptor, close to position 5 of NKA. This would facilitate interaction with positively charged side chains and impede interaction with negatively charged side chains, particularly the inflexible side chain of aspartic acid. Thus,not only the charge, but also the length of the side chain of the residue at position 5, seems to be important for interaction with the rat NK2 receptor.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/03/20 alle ore 11:30:33