Highly potent nociceptin analog containing the Arg-Lys triple repeat.
Highly potent nociceptin analog containing the Arg-Lys triple repeat.
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含有 Arg-Lys 三重重复序列的高效伤害感受肽类似物。
DOI：
10.1006/bbrc.2000.3822
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发表时间：
2000
影响因子：
3.1
通讯作者：
Y. Shimohigashi
中科院分区：
文献类型：
--
作者：
K. Okada;T. Sujaku;Y. Chuman;R. Nakashima;T. Nose;T. Costa;Yoshinari Yamada;Masayuki Yokoyama;A. Nagahisa;Y. Shimohigashi
神经肽伤害感受肽的结构特征之一是在位置 8-9 和 12-13 处存在 Arg-Lys (RK) 残基；两种 RK 均被认为与七跨膜结构域受体 ORL1 的第二个胞外环中的酸性氨基酸簇结合。通过尝试获得与受体酸性簇结合更牢固的类似物的设计策略，我们合成了一系列伤害感受素类似物，其中 RK 二肽单元位于与亲本 RK 相邻的位置 6-7、10-11 或 14-15。在这些含有 RK 三重重复序列的伤害感受肽类似物中，[Arg-Lys(6-7)]- 和 [Arg-Lys(10-11)] 伤害感受肽在受体结合测定和 [(35)S]GTPgammaS 结合功能测定中均表现出弱活性（分别为伤害感受肽的 6-9% 和 60-90%）。相比之下，[Arg-Lys(14-15)]nociceptin 在两种测定中均非常有效（结合力为 3 倍，GTPgammaS 功能测定为 17 倍）。 [Arg-Lys(14-15)]伤害感受肽是第一个被发现比母体伤害感受肽更强的肽类似物，结构活性研究表明，掺入的 Arg-Lys(14-15) 与受体酸性氨基酸簇或受体芳香氨基酸残基相互作用。
One of the structural characteristics of a neuropeptide nociceptin is the existence of Arg-Lys (RK) residues at positions 8-9 and 12-13; both RKs have been suggested to bind to the acidic amino acid cluster in the second extracellular loop of the seven transmembrane domain receptor ORL1. With a design strategy of attempting to obtain an analog that binds more strongly to the receptor's acidic cluster, we synthesized a series of nociceptin analogs in which the RK dipeptide unit was placed at positions 6-7, 10-11, or 14-15 adjacent to the parent RKs. Among these nociceptin analogs containing the RK triple repeat, [Arg-Lys(6-7)]- and [Arg-Lys(10-11)]nociceptins exhibited weak activities (6-9 and 60-90% of nociceptin, respectively) both in the receptor binding assay and in the [(35)S]GTPgammaS binding functional assay. In contrast, [Arg-Lys(14-15)]nociceptin was found to be very potent in both assays (3-fold in binding and 17-fold in GTPgammaS functional assay). [Arg-Lys(14-15)]nociceptin was the first peptide analog found to be stronger than the parent nociceptin, and structure-activity studies have suggested that the incorporated Arg-Lys(14-15) interacts with either the receptor acidic amino acid cluster or the receptor aromatic amino acid residues.
编码小鼠脑孤啡肽 FQ/伤害感受素前体的 cDNA 的克隆和表达。
DOI：
10.1042/bj3150011
发表时间：
1996
期刊：
The Biochemical journal
影响因子：
--
作者：
Pan,YX;Xu,J;Pasternak,GW
通讯作者：
Pasternak,GW