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 aquated metabolite (DDP-OH) on a dimyristoylphosphatidylserine (DMPS) model membrane was investigated by pressure tuning vibrational spectroscopy. The native species (DDP-Cl) and the aquated species (DPP-OH) were both observed to bind to the carboxylate group of the serine as evidenced by a frequency shift of 1622-1620 cm-1. However, only DDP-OH was observed to bind to the phosphate group (PO(-)2). The binding of either 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 were increased. The two drugs did not partition into the matrix of the hydrophobic section in the model membrane. Collectively, these data suggest that DDP-Cl and DDP-OH are capable of binding to the polar head group of DMPS, resulting in an enlargement of the area of the head and a subsequent increase in the intermolecular distance between the acyl chains.
Ottawa Regional Cancer Centre, Canada.
K D
KD
Taylor
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R
Goel
F H
FH
Shirazi
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M
Molepo
P
P
Popovic
D J
DJ
Stewart
P T
PT
Wong
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D002945:Cisplatin / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D008051:Lipid Bilayers / Q000737:chemistry; D008567:Membranes, Artificial; D010718:Phosphatidylserines / Q000737:chemistry* / Q000378:metabolism; D011312:Pressure; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods
D000970:Antineoplastic Agents; D008051:Lipid Bilayers; D008567:Membranes, Artificial; D010718:Phosphatidylserines; C042859:dimyristoylphosphatidylserine; D002945:Cisplatin