当前位置：
X-MOL 学术
›
Cell Chem. Bio.
›
论文详情
Our official English website, www.x-mol.net, welcomes your
feedback! (Note: you will need to create a separate account there.)
Identification of Chemotype Agonists for Human Resolvin D1 Receptor DRV1 with Pro-Resolving Functions.
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2018-12-13 , DOI: 10.1016/j.chembiol.2018.10.023
Nan Chiang 1 , Elena Barnaeva 2 , Xin Hu 2 , Juan Marugan 2 , Noel Southall 2 , Marc Ferrer 2 , Charles N Serhan 1
Cell Chemical Biology ( IF 6.6 ) Pub Date : 2018-12-13 , DOI: 10.1016/j.chembiol.2018.10.023
Nan Chiang 1 , Elena Barnaeva 2 , Xin Hu 2 , Juan Marugan 2 , Noel Southall 2 , Marc Ferrer 2 , Charles N Serhan 1
Affiliation
|
Resolution of acute inflammation is governed, in part, by specialized pro-resolving mediators, including lipoxins, resolvins, protectins, and maresins. Among them, resolvin D1 (RvD1) exhibits potent pro-resolving functions via activating human resolvin D1 receptor (DRV1/GPR32). RvD1 is a complex molecule that requires challenging organic synthesis, diminishing its potential as a therapeutic. Therefore, we implemented a high-throughput screening of small-molecule libraries and identified several chemotypes that activated recombinant DRV1, represented by NCGC00120943 (C1A), NCGC00135472 (C2A), pMPPF, and pMPPI. These chemotypes also elicited rapid impedance changes in cells overexpressing recombinant DRV1. With human macrophages, they each stimulated phagocytosis of serum-treated zymosan at concentrations comparable with that of RvD1, the endogenous DRV1 ligand. In addition, macrophage phagocytosis of live E. coli was significantly increased by these chemotypes in DRV1-transfected macrophages, compared with mock-transfected cells. Taken together, these chemotypes identified by unbiased screens act as RvD1 mimetics, exhibiting pro-resolving functions via interacting with human DRV1.
中文翻译：
具有前分辨功能的人Resolvin D1受体DRV1的化学激动剂的鉴定。
急性炎症的解决部分由专门的促分辨介质（包括脂蛋白，分辨素，保护素和马林素）控制。其中，resolvin D1（RvD1）通过激活人的resolvin D1受体（DRV1 / GPR32）表现出强大的促分解功能。RvD1是一个复杂的分子，需要具有挑战性的有机合成，从而削弱了其作为治疗剂的潜力。因此，我们实施了小分子文库的高通量筛选，并鉴定了激活重组DRV1的几种化学型，以NCGC00120943（C1A），NCGC00135472（C2A），pMPPF和pMPPI表示。这些化学型还引起过表达重组DRV1的细胞中的快速阻抗变化。在人类巨噬细胞中，它们各自以与RvD1相当的浓度刺激血清处理的酵母聚糖的吞噬作用，内源性DRV1配体。此外，与模拟转染的细胞相比，DRV1转染的巨噬细胞中这些化学型显着提高了活大肠杆菌的巨噬细胞吞噬能力。综上所述，通过无偏性筛选鉴定出的这些化学型可作为RvD1模拟物，通过与人类DRV1相互作用表现出亲分辨功能。
更新日期：2019-02-22
中文翻译：
具有前分辨功能的人Resolvin D1受体DRV1的化学激动剂的鉴定。
急性炎症的解决部分由专门的促分辨介质（包括脂蛋白，分辨素，保护素和马林素）控制。其中，resolvin D1（RvD1）通过激活人的resolvin D1受体（DRV1 / GPR32）表现出强大的促分解功能。RvD1是一个复杂的分子，需要具有挑战性的有机合成，从而削弱了其作为治疗剂的潜力。因此，我们实施了小分子文库的高通量筛选，并鉴定了激活重组DRV1的几种化学型，以NCGC00120943（C1A），NCGC00135472（C2A），pMPPF和pMPPI表示。这些化学型还引起过表达重组DRV1的细胞中的快速阻抗变化。在人类巨噬细胞中，它们各自以与RvD1相当的浓度刺激血清处理的酵母聚糖的吞噬作用，内源性DRV1配体。此外，与模拟转染的细胞相比，DRV1转染的巨噬细胞中这些化学型显着提高了活大肠杆菌的巨噬细胞吞噬能力。综上所述，通过无偏性筛选鉴定出的这些化学型可作为RvD1模拟物，通过与人类DRV1相互作用表现出亲分辨功能。
京公网安备 11010802027423号