Barlow P N, Vidal J C, Lister M D, Hancock A J, Sigler P B
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.
Chem Phys Lipids. 1988 Mar;46(3):157-64. doi: 10.1016/0009-3084(88)90017-5.
Reported herein is the synthesis of (+)- and (-)-(1,3/2)-1-O-(phosphocholine)-2,3-O-dihexanoylcyclopentane-1,2, 3-triol. These are the enantiomers of a contrained analogue of dihexanoylphosphatidylcholine in which the glycerol backbone is replaced by all-trans cyclopentane-1,2,3-triol. Evidence is presented to demonstrate that the (-)-enantiomer is a substrate for phospholipase A2 (PLA2) (Crotalus atrox) while the (+)-enantiomer is not. This strict enantiomeric (and positional) specificity was exploited in conjunction with a novel application of DEAE-cellulose column chromatography, to achieve racemic resolution with an excellent yield. The constrained backbone geometry, and the experimentally accessible critical micellar concentration (CMC) of these analogues should render them useful probes for assessing the contribution of substrate conformation and flexibility to the catalytic efficiency of PLA2.
本文报道了(+)-和(-)-(1,3/2)-1-O-(磷酰胆碱)-2,3-O-二己酰基环戊烷-1,2,3-三醇的合成。它们是二己酰基磷脂酰胆碱的一种受限类似物的对映体，其中甘油主链被全反式环戊烷-1,2,3-三醇取代。有证据表明(-)-对映体是磷脂酶A2（响尾蛇毒）的底物，而(+)-对映体不是。这种严格的对映体（和位置）特异性与DEAE-纤维素柱色谱的一种新应用相结合，以优异的产率实现了外消旋体拆分。这些类似物的受限主链几何结构以及实验可获得的临界胶束浓度（CMC）应使它们成为评估底物构象和柔韧性对磷脂酶A2催化效率贡献的有用探针。
