Effects of Substitution of Hydrophobic Amino Acids by Tryptophan on Receptor Binding and Biological Activity of Neuropeptide Nociceptin
Effects of Substitution of Hydrophobic Amino Acids by Tryptophan on Receptor Binding and Biological Activity of Neuropeptide Nociceptin
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色氨酸取代疏水性氨基酸对神经肽痛敏肽受体结合及生物活性的影响
DOI：
10.1246/bcsj.72.1899
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发表时间：
1999
影响因子：
4
通讯作者：
Y. Shimohigashi
中科院分区：
文献类型：
--
作者：
K. Okada;T. Sujaku;R. Nakashima;T. Nose;Yoshinari Yamada;Masayuki Yokoyama;A. Nagahisa;Y. Shimohigashi
痛敏肽是一种神经肽，可结合并激活类阿片受体 ORL1 受体。为了探索受体识别和激活所必需的结构元件，我们设计并合成了一系列伤害感受肽类似物，其中Gly6、Ala7、Ala11、Leu14和Ala15等非极性氨基酸残基分别被Trp取代。 [Trp6]-和[Trp7]伤害感受肽表现出相当弱的活性（伤害感受肽的5-15%），并且[Trp11]-和[Trp15]伤害感受肽也表现出降低的活性（40-50%）。这些结果表明这些特定残基的可用空间相对有限。相比之下，14位的Trp/Leu取代保留了完整的受体结合活性，并且所得的[Trp14]伤害感受肽在使用[35S]GTPγS的功能测定中表现出增加的生物活性。这表明与痛敏肽-Leu14相互作用的受体残基是芳香族氨基酸。
Nociceptin is a neuropeptide that binds to and activates the opioid receptor-like ORL1 receptor. In order to explore the structural elements necessary for receptor recognition and activation, we designed and synthesized a series of nociceptin analogues, in which nonpolar amino acid residues such as Gly6, Ala7, Ala11, Leu14, and Ala15were substituted respectively by Trp. [Trp6]- and [Trp7]nociceptins exhibited rather weak activities (5—15% of nociceptin), and [Trp11]- and [Trp15]nociceptins also showed reduced activities (40—50%). These results suggested that the space available for these particular residues are relatively restricted. By contrast, the Trp/Leu-substitution at position 14 retained full receptor binding activity, and the resulting [Trp14]nociceptin exhibited an increased biological activity in the functional assay using [35S]GTPγS. This suggested that the receptor residue interacting with nociceptin-Leu14 is the aromatic amino acid.