Kd. Taylor et al., PRESSURE TUNING INFRARED SPECTROSCOPIC STUDY OF CISPLATIN-INDUCED STRUCTURAL-CHANGES IN A PHOSPHATIDYLSERINE MODEL MEMBRANE, British Journal of Cancer, 72(6), 1995, pp. 1400-1405
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.