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 ((PCPC14)-P-1 4 and (PCPC16)-P-16), which have packing behavior, melting temperatures, an d monomer unit structures that mimic those of I,2-dimyristoyl-sn-glycero-3- phosphocholine (DMPC) and 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC ). Examination of the mixing behavior of pC(16) and analogous phosphatidylg lycerol (PG) mimic, by use of the nearest-neighbor recognition method, has revealed that these Lipids are ideally miscible in the physiologically rele vant fluid phase. Addition of a hydrocarbon chain length mismatch of four m ethylenes per acyl chain and/or the addition of 29 mol % cholesterol do not alter such miscibility. In contrast, the inclusion of a basic peptide (pen talysine) affords a modest degree of nearest-neighbor recognition. The intr oduction of exchangeable phospholipid dimers that mimic phosphatidylcholine s significantly expands the scope of the nearest-neighbor recognition metho d and increases its relevance to the study of animal cell membranes, whose two-dimensional structures remain to be elucidated.