Design and Synthesis of Phosphatidylcholine Mimics and Their Mixing Behavior with Phosphatidylglycerol Mimics in the Fluid Bilayer State

Two disulfide-based phospholipid dimers have been synthesized (PC14PC14 and PC16PC16), which have packing behavior, melting temperatures, and monomer unit structures that mimic those of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC). Examination of the mixing behavior of PC16 and an analogous phosphatidylglycerol (PG) mimic, by use of the nearest-neighbor recognition method, has revealed that these lipids are ideally miscible in the physiologically relevant fluid phase. Addition of a hydrocarbon chain length mismatch of four methylenes per acyl chain and/or the addition of 29 mol % cholesterol do not alter such miscibility. In contrast, the inclusion of a basic peptide (pentalysine) affords a modest degree of nearest-neighbor recognition. The introduction of exchangeable phospholipid dimers that mimic phosphatidylcholines significantly expands the scope of the nearest-neighbor recognition method and increases its relevance to the study of animal c...