5LP1

CRYSTAL STRUCTURE OF HUMAN LIPOPROTEIN-ASSOCIATED PHOSPHOLIPASE A2 IN COMPLEX WITH A [1.1.1]BICYCLOPENTANE-CONTAINING INHIBITOR AT 1.91A RESOLUTION.

5LP1 の概要

• エントリーDOI: 10.2210/pdb5lp1/pdb
• 分子名称: Platelet-activating factor acetylhydrolase, CHLORIDE ION, ~{N}-[2-(diethylamino)ethyl]-2-[2-[(4-fluorophenyl)methylsulfanyl]-4-oxidanylidene-5~{H}-cyclopenta[d]pyrimidin-1-yl]-~{N}-[[3-[4-(trifluoromethyl)phenyl]-1-bicyclo[1.1.1]pentanyl]methyl]ethanamide, ... (4 entities in total)
• 機能のキーワード: plasma platelet-activating factor acetylhydrolase, secreted protein, alpha/beta-hydrolase-fold, ldl-bound; lipoprotein associated phospholipase a2, lp-pla2, group viia pla2, glycoprotein, hydrolase, lipid degradation, polymorphism, secreted, hydrolase-hydrolase inhibitor complex, hydrolase/hydrolase inhibitor
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 44928.80

構造登録者

Somers, D. (登録日: 2016-08-11, 公開日: 2017-02-01, 最終更新日: 2024-05-01)

主引用文献

Measom, N.D.,Down, K.D.,Hirst, D.J.,Jamieson, C.,Manas, E.S.,Patel, V.K.,Somers, D.O.
Investigation of a Bicyclo[1.1.1]pentane as a Phenyl Replacement within an LpPLA2 Inhibitor.
ACS Med Chem Lett, 8:43-48, 2017

PubMed Abstract: We describe the incorporation of a bicyclo[1.1.1]pentane moiety within two known LpPLA inhibitors to act as bioisosteric phenyl replacements. An efficient synthesis to the target compounds was enabled with a dichlorocarbene insertion into a bicyclo[1.1.0]butane system being the key transformation. Potency, physicochemical, and X-ray crystallographic data were obtained to compare the known inhibitors to their bioisosteric counterparts, which showed the isostere was well tolerated and positively impacted on the physicochemical profile.

PubMed: 28105273
DOI: 10.1021/acsmedchemlett.6b00281

実験手法

X-RAY DIFFRACTION (1.91 Å)