Synthesis and some properties of constrained short-chain phosphatidylcholine analogues: (+)- and (-)-(1,3/2)-1-O-(phosphocholine)2,3-O- dihexanoylcyclopentane-1,2,3-triol.
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.
Barlow
P N
PN
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.
Vidal
J C
JC
Lister
M D
MD
Hancock
A J
AJ
Sigler
P B
PB
D002855:Chromatography, Thin Layer; D003435:Crotalid Venoms; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D010713:Phosphatidylcholines / Q000138:chemical synthesis*; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D003435:Crotalid Venoms; D007202:Indicators and Reagents; D010713:Phosphatidylcholines; C056170:1-O-(phosphocholine)-2,3-O-dihexanoylcyclopentane-1,2,3-triol; D010741:Phospholipases A; D054467:Phospholipases A2