Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists.
Functional characterization of five different PRXamide receptors of the red flour beetle Tribolium castaneum with peptidomimetics and identification of agonists and antagonists.
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用拟肽对红谷甲赤拟谷盗五种不同的 PRXamide 受体进行功能表征以及激动剂和拮抗剂的鉴定
DOI：
10.1016/j.peptides.2014.11.004
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发表时间：
2015-06
期刊：
影响因子：
3
通讯作者：
Park Y
中科院分区：
文献类型：
--
作者：
Jiang H;Wei Z;Nachman RJ;Kaczmarek K;Zabrocki J;Park Y
昆虫的神经肽能系统是害虫防治策略的一个很好的靶标。一种有前途的生物合理的方法是使用从内源性配体修饰的肽模拟物来增强生物稳定性和生物利用度。在这项研究中，我们的功能特点是5个不同的G蛋白偶联受体在一个系统发育的集群，包含受体PRXamide在红粉甲虫赤拟谷盗，通过评估一系列的70种不同的肽和肽模拟物。本研究包括三种焦激肽受体（TcPKr-A、-B和-C）、心脏加速肽受体（TcCAPAr）和蜕皮触发激素受体（TcETHR）。鉴定了强激动性或拮抗性肽模拟物，包括核心氨基酸残基脯氨酸的β-脯氨酸（β 3 P）修饰以及环肽。配体作用于多个受体是常见的。在许多情况下，作为一种受体的激动剂的配体是另一种受体的有效拮抗剂，这表明肽模拟物在生物系统中的复杂结果。有趣的是，TcPK-A与大量激动剂高度混杂，而TcPK-C和TcCAPAr具有较低数量的激动剂，但具有较高数量的化合物作为拮抗剂。这一观察结果表明，具有更多混杂性的靶GPCR将为拟肽方法提供更好的成功。这项研究是首次描述的肽模拟物的CAPA受体，并导致肽模拟物类似物，证明CAPA配体的拮抗作用的鉴定。使用肽模拟物的PRXamide受体测定提供了对受体生化特性的有用见解。
The neuropeptidergic system in insects is an excellent target for pest control strategies. One promising biorational approach is the use of peptidomimetics modified from endogenous ligands to enhance biostability and bioavailability. In this study, we functionally characterized five different G protein-coupled receptors in a phylogenetic cluster, containing receptors for PRXamide in the red flour beetle Tribolium castaneum, by evaluating a series of 70 different peptides and peptidomimetics. Three pyrokinin receptors (TcPKr-A, -B, and –C), cardioacceleratory peptide receptor (TcCAPAr) and ecdysis triggering hormone receptor (TcETHr) were included in the study. Strong agonistic or antagonistic peptidomimetics were identified, and included beta-proline (β3P) modification of the core amino acid residue proline and also a cyclo-peptide. It is common for a ligand to act on multiple receptors. In a number of cases, a ligand acting as an agonist on one receptor was an efficient antagonist on another receptor, suggesting complex outcomes of a peptidomimetic in a biological system. Interestingly, TcPK-A was highly promiscuous with a high number of agonists, while TcPK-C and TcCAPAr had a lower number of agonists, but a higher number of compounds acting as an antagonist. This observation suggests that a target GPCR with more promiscuity will provide better success for peptidomimetic approaches. This study is the first description of peptidomimetics on a CAPA receptor and resulted in the identification of peptidomimetic analogs that demonstrate antagonism of CAPA ligands. The PRXamide receptor assays with peptidomimetics provide useful insights into the biochemical properties of receptors.
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影响因子：
3.8
作者：
Aikins, Michael J.;Schooley, David A.;Park, Yoonseong
通讯作者：
Park, Yoonseong
影响因子：
3
作者：
Nachman, Ronald J.;Wang, Xiaodong J.;Altstein, Miriam
通讯作者：
Altstein, Miriam
影响因子：
3
作者：
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影响因子：
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作者：
Kim, Young-Joon;Zitnan, Dusan;Adams, Michael E.
通讯作者：
Adams, Michael E.
影响因子：
3
作者：
Jiang H;Wei Z;Nachman RJ;Park Y
通讯作者：
Park Y