Ferrari Cristina, Macchiarulo Antonio, Costantino Gabriele, Pellicciari Roberto
Dipartimento di Chimica e Tecnologia del Farmaco, Università di Perugia, via del Liceo 1, 06127 Perugia, Italy.
J Comput Aided Mol Des. 2006 May;20(5):295-303. doi: 10.1007/s10822-006-9055-1. Epub 2006 Sep 14.
Formyl-peptide receptors (FPRs) belong to the family A of the G-protein coupled receptor superfamily and include three subtypes: FPR, FPR-like-1 and FPR-like-2. They have been involved in the control of many inflammatory processes promoting the recruitment and infiltration of leukocytes in regions of inflammation through the molecular recognition of chemotactic factors. A large number of structurally diverse chemotypes modulate the activity of FPRs. Newly identified antagonists include bile acids deoxycholic acid (DCA) and chenodeoxycholic acid (CDCA). The molecular recognition of these compounds at FPR receptor was computationally investigated using both ligand- and structure-based approaches. Our findings suggest that all antagonists bind at the first third of the seven helical bundles. A closer inspection of bile acid interaction reveals a number of unexploited anchor points in the binding site that may be used to aid the design of new potent and selective bile acids derivatives at FPR.
甲酰肽受体（FPRs）属于G蛋白偶联受体超家族A类，包括三种亚型：FPR、FPR样-1和FPR样-2。它们参与了许多炎症过程的调控，通过对趋化因子的分子识别促进白细胞在炎症区域的募集和浸润。大量结构多样的化学型调节FPRs的活性。新发现的拮抗剂包括胆汁酸脱氧胆酸（DCA）和鹅脱氧胆酸（CDCA）。使用基于配体和结构的方法对这些化合物在FPR受体上的分子识别进行了计算研究。我们的研究结果表明，所有拮抗剂都结合在七螺旋束的前三分之一处。对胆汁酸相互作用的进一步研究揭示了结合位点中一些未被利用的锚定点，这些锚定点可用于辅助设计新型强效且选择性的FPR胆汁酸衍生物。
