Three-Dimensional Consensus Structure of sst2-Selective Somatostatin (SRIF) Antagonists by NMR
Three-Dimensional Consensus Structure of sst2-Selective Somatostatin (SRIF) Antagonists by NMR
复制标题
DOI：
10.1002/bip.21060
复制
发表时间：
2008-12-01
期刊：
影响因子：
2.9
通讯作者：
Riek, Roland
中科院分区：
文献类型：
--
作者：
Grace, Christy Rani R.;Erchegyi, Judit;Riek, Roland
以奥曲肽（octreotide）为基础，合成了7个生长抑素八肽类似物（SRIF），其基本序列为H-Cpa/Phe（2）-c[DCys（3）-Xxx（7）-DTrp/DAph（Cbm）（8）-Lys（9）-Thr（10）-Cys（14）]-Yyy-NH_2（编号是指天然SRIF中的位置），其中Xxx（7）是Aph（Cbm）/Tyr/Agl（NMe，苯甲酰基），Yyy是Nal/DTyr/Thr。这些类似物中的大多数表现出对sst（2）受体的强有力的和高选择性的结合，并且所有的类似物都是抑制受体信号传导的拮抗剂。基于它们的共有三维结构，确定了sst（2）-选择性拮抗剂的药效团。药效团包括Cpa（2）、DTrp/DAph（Cbm）（8）和Lys（9）的侧链，其主链为之前描述的大多数sst（2）-选择性拮抗剂药效团。(C)2008 Wiley Periodicals，Inc. Biopolymers 89：1077-1087，2008.
The three-dimensional NMR structures of seven octapeptide analogs of somatostatin (SRIF), based on octreotide, with the basic sequence H-Cpa/Phe(2)-c[DCys(3)-Xxx(7)-DTrp/DAph(Cbm)(8)-Lys(9)-Thr(10)-Cys(14)]-Yyy-NH2 (the numbering refers to the position in native SRIF), with Xxx(7) being Aph(Cbm)/Tyr/Agl(NMe,benzoyl) and Yyy being Nal/DTyr/Thr, are presented here. Most of these analogs exhibit potent and highly selective binding to sst(2) receptors, and all of the analogs are antogonists inhibiting receptor signaling. Based on their consensus 3D structure, the pharmacophore of the sst(2)-selective antagonist has been defined. The pharmacophore involves the side chains of Cpa(2), DTrp/DAph(Cbm)(8), and Lys(9), with the backbone for most of the sst(2)-selective antagonist pharmacophore previously described. (C) 2008 Wiley Periodicals, Inc. Biopolymers 89: 1077-1087, 2008.