PRESSURE TUNING INFRARED SPECTROSCOPIC STUDY OF CISPLATIN-INDUCED STRUCTURAL-CHANGES IN A PHOSPHATIDYLSERINE MODEL MEMBRANE

The dynamic effect of cis-diamminedichloroplatinum(II) (DPP) and its a quated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) m odel membrane was investigated by pressure tuning vibrational spectros copy. The native species (DDP-Cl) and the aquated species (DPP-OH) wer e both observed to bind to the carboxylate group of the serine as evid enced by a frequency shift of 1622-1620 cm(-1). However, only DDP-OH w as observed to bind to the phosphate group (PO2-). The binding of eith er drug to DMPS resulted in an increased pressure required to halt the reorientational fluctuations of the acyl chains, indicating that the distance between the chains was increased. The two drugs did not parti tion into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable o f binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecul ar distance between the acyl chains.