Synthesis and Properties of Radioiodinated Phospholipid Analogues That Spontaneously Undergo Vesicle-Vesicle and Vesicle-Cell Transfer

An efficient method for the synthesis and purification of a variety of iodinated phospholipid analogues is described. 1-Acyl-2-[[[3-(3-[¹²⁵I] iodo-4-hydroxyphenyl)-propionyl]amino]caproyl]phosphatidylcholine (¹²⁵I-PC) was prepared by alkylation of 1-acyl-2-(aminocaproyl)phosphatidylcholine with monoiodinated Bolton-Hunter reagent. ¹²⁵I-Labeled phosphatidic acid, phosphatidylethanolamine, and phosphatidylserine were produced from ¹²⁵I-PC by phospholipase D catalyzed base exchange in the presence of ethanol-amine or l-serine. All of these lipid analogues transferred readily from donor vesicles into recipient membranes. When an excess of acceptor vesicles was mixed with a population of donor vesicles containing the iodinated analogues, approximately 50% of the ¹²⁵I-labeled lipids transferred to the acceptor vesicle population. In addition, under appropriate incubation conditions, these lipids were observed to transfer from vesicles to mammalian cells. Autoradiographic analysis of ¹²⁵I-labeled lipids extracted from the cells after incubation with vesicles at 2 °C for 60 min revealed that a large proportion of the ¹²⁵I-labeled phosphatidic acid was metabolized to ¹²⁵I-labeled diglyceride and ¹²⁵I-labeled phosphatidylcholine, whereas no metabolism of exogenously supplied ¹²⁵I-labeled phosphatidylethanolamine or ¹²⁵I-labeled phosphatidylcholine could be detected.