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首页> 外文期刊>Journal of Biomolecular Structure and Dynamics >Correlation of secondary structures of bradykinin b1 receptor antagonists with their activity.
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Correlation of secondary structures of bradykinin b1 receptor antagonists with their activity.

机译:缓激肽b1受体拮抗剂的二级结构与其活性的关系。

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The secondary structure of a bradykinin B(1)receptor antagonist B-10324 (F5C-Lys-(1)- Lys(0)-Arg(1)-Pro(2)- Hyp(3)-Gly(4)-CpG(5)- Ser(6)-DTic(7)-CpG(8)) was determined by NMR at 800MHz. The conformational data are compared with those obtained previously for two bradykinin B(1) receptor antagonists, namely B-9858 (Lys-(1)- Lys(0)-Arg(1)-Pro(2)- Hyp(3)-Gly(4)-Igl(5)- Ser(6)-DIgl(7)-Oic(8)) and B-10148 (Lys-(1)-Lys(0)-Arg(1)- Pro(2)-Hyp(3)-Gly(4)- Igl(5)-Ser(6)-DF5F(7)- Oic(8)). The abnormal amino acids are: Hyp, trans-4- hydroxyproline; Tic, 1, 2, 3, 4-tetrahydroisoquinoline-3-carboxylic acid; Oic, (2S, 3aS, 7aS)-octahydroindole-2-carboxylic acid; Igl, alpha(2- indanyl)glycine; F5F, 2,3,4,5,6-pentafluorophenylalanine; CpG, alpha- cyclopentylglycine. F5C, pentafluorocinnamoyl, is the N-terminal protecting group and is not involved in the peptide secondary structure. B-10324 contains an N-terminal Pro(2)- CpG(5) distorted type II beta-turn whereas the rest of the peptide is random. A salt bridge is not observed between the carboxylate group at the C-terminal end and the Arg(1) side chain, in contrast to that previously observed for B-9858 and B- 10148. The conformations are correlated with the measured B(1) receptor antagonist activities (J.-F. Larrivee, L. Gera, S. Houle, J. Bouthillier, D. R. Bachvarov, J. M. Stewart and F. Marc au, Br. J. Pharmacol. 131, 885-892 (2000)). The importance of the N-terminal beta-turn is highlighted.
机译:缓激肽B(1)受体拮抗剂B-10324(F5C-Lys-(1)-Lys(0)-Arg(1)-Pro(2)-Hyp(3)-Gly(4)-CpG的二级结构通过NMR在800MHz下测定(5)-Ser(6)-DTic(7)-CpG(8)。将构象数据与先前获得的两种缓激肽B(1)受体拮抗剂B-9858(Lys-(1)-Lys(0)-Arg(1)-Pro(2)-Hyp(3)- Gly(4)-Igl(5)-Ser(6)-DIgl(7)-Oic(8))和B-10148(Lys-(1)-Lys(0)-Arg(1)-Pro(2) -Hyp(3)-Gly(4)-Igl(5)-Ser(6)-DF5F(7)-Oic(8))。异常氨基酸为:Hyp,反式-4-羟脯氨酸; Tic,1,2,3,4-四氢异喹啉-3-羧酸; Oic,(2S,3aS,7aS)-八氢吲哚-2-羧酸; Igl,α(2-茚满基)甘氨酸; F5F,2,3,4,5,6-五氟苯丙氨酸; CpG,α-环戊基甘氨酸。 F5C,五氟肉桂酰基,是N端保护基,不参与肽的二级结构。 B-10324包含一个N端Pro(2)-CpG(5)扭曲的II型β-转角,而其余肽段是随机的。与以前在B-9858和B-10148中观察到的相反,在C末端的羧酸酯基团和Arg(1)侧链之间未观察到盐桥。构象与测得的B(1)相关受体拮抗剂活性(J.-F. Larrivee,L.Gera,S.Houle,J.Bouthillier,DR Bachvarov,JM Stewart和F.Marc au,Br.J.Pharmacol.131,885-892(2000)) 。强调了N端beta旋转的重要性。

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