CYCLIC SOMATOSTATIN OCTAPEPTIDE ANALOGS WITH HIGH-AFFINITY AND SELECTIVITY TOWARD MU OPIOID RECEPTORS
CYCLIC SOMATOSTATIN OCTAPEPTIDE ANALOGS WITH HIGH-AFFINITY AND SELECTIVITY TOWARD MU OPIOID RECEPTORS
复制标题
DOI：
10.1016/0024-3205(86)90574-6
复制
发表时间：
1986-06-16
期刊：
影响因子：
6.1
通讯作者：
YAMAMURA, HI
中科院分区：
文献类型：
--
作者：
GULYA, K;PELTON, JT;YAMAMURA, HI
已通过标准固相合成技术制备了一系列含有生长抑素八肽类似物的环状构象受限青霉胺，并测试了它们抑制特异性[125 I]CGP 23，996（des-Ala 1-，Gly 2-[desamino-Cys 3 Tyr 11]-dicarba 3，14生长抑素）、[3 H]纳洛酮或[3 H]DPDPE的能力。图形 **。大鼠脑细胞膜制备物中的结合。我们现在报告我们最有效和选择性的μ阿片受体化合物的合成的结构-活性关系研究。图形 **。我们称之为Cys 2 Tyr 3 Orn 5 Pen 7-酰胺。虽然该八肽对明显单一的结合位点群体（nH = 0.89 ± 0.001）表现出高亲和力（IC 50 = 2.80 nM）。0.1)对μ阿片受体的选择性非常高，IC 50（DPDPE）/IC 50（纳洛酮）比值为4，829，但对生长抑素受体的亲和力也非常低（IC 50 = 22，700 nM）。因此，Cys 2 Tyr 3 Orn 5 Pen 7-酰胺可能是进一步表征μ阿片受体和检查这类受体的生理作用的配体的选择。
A series of cyclic conformationally restricted penicillamine containing somatostatin octapeptide analogues have been prepared by standard solid phase synthetic techniques and tested for their ability to inhibit specific [125I]CGP 23,996 (des-Ala1-,Gly2-[desamino-Cys3Tyr11]-dicarba3,14 somatostatin), [3H]naloxone or [3H]DPDPE .**GRAPHIC**. binding in rat brain membrane preparations. We now report structure-activity relationship studies with the synthesis of our most potent and selective mu opioid receptor compound .**GRAPHIC**. which we refer to be Cys2Tyr3Orn5Pen7-amide. While this octapeptide exhibited high affinity (IC50 = 2.80 nM) for an apparently single population of binding sites (nH = 0.89 .+-. 0.1) and exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50 (naloxone) ratio of 4,829, it also displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM). Thus, Cys2Tyr3Orn5 Pen7-amide may be the ligand of choice for further characterization of mu opioid receptors and for examining the physiological role of this class of receptors.