Abstract:
A novel class of phospholipase-resisting phosphatidylcholine analogs, in which the C-2 ester group or both C-1 and C-2 ester groups have been replaced by carbamyloxy functions (-NH-C-O-), have been synthesized. These lipids were
not degraded by phospholipase A2 while complete hydrolysis occurred with
phospholipase C. Ultrasonic irradiation of the aqueous dispersions of the phospholipids
in the presence as well as in the absence of cholesterol resulted in the
formation of closed bilayer structures as evidenced by negative staining electron
microscopy and also by their ability to entrap [14C]glucose. The leakage
rates of glucose at 37°C from liposomes of these compounds have also been
measured. Liposomes consisting of 1,2-dipentadecanylcarbamyloxy-sn-glycero-
3-phosphorylcholine were found to be more leaky (2.1 %/h) as compared to the
liposomes of 1-palmitoyl-2-pentadecanylcarbamyloxy-sn -glycero-3-phosphoryl- choline (O.5%/h). Moreover, inclusion of cholesterol (33 mol%) into the bilayers of the former phospholipid had no effect on the leakage rate (2.4%/h) while it
effectively reduced permeability of the latter (O.22%/h). These phosphatidylcholines
are useful for studying the possible role of phospholipases in the capture
and lysis of liposomes in vivo.
