1H NMR investigation on interaction between ibuprofen and lipoproteins.
A large number of studies indicate that oxidative modification of plasma lipoproteins, especially low-density lipoprotein (LDL), is a critical factor in initiation and progression of atherosclerosis. We have previously found that ibuprofen (IBP), a potential antioxidant drug to inhibit LDL oxidation, interacted with lipoproteins in intact human plasma. In the present study, we compare the binding affinities of IBP to LDL and HDL (high-density lipoprotein) by (1)H NMR spectroscopy. When IBP is added into the HDL and LDL samples, the - N(+)(CH(3))(3) moieties of phosphatidylcholine (PC) and sphingomyelin (SM) in lipoprotein particles experience the chemical shift up-field drift. Intermolecular cross-peaks observed in NOESY spectra imply that there are direct interactions between ibuprofen and lipoproteins at both hydrophobic and hydrophilic (ionic) regions. These interactions are likely to be important in the solubility of ibuprofen into lipoprotein particles. Ibuprofen has higher impact on the PC and SM head group ( - N(+)(CH(3))(3)) and - (CH(2))(n) - group in HDL than that in LDL. This could be explained by either IBP has higher binding affinity to HDL than to LDL, or IBP induces orientation of the phospholipid head group at the surface of the lipoprotein particles.
Lan
Wenxian
W
Wuhan Center for Magnetic Resonance, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Wuhan Institute of Physics and Mathematics, Chinese Academy of Sciences, Wuhan 430071, PR China.
Zhu
Hang
H
Zhou
Zhiming
Z
Ye
Chaohui
C
Liu
Maili
M
D000975:Antioxidants / Q000494:pharmacology*; D001665:Binding Sites; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007052:Ibuprofen / Q000737:chemistry* / Q000378:metabolism; D008074:Lipoproteins / Q000737:chemistry* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000737:chemistry / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D010084:Oxidation-Reduction; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D012995:Solubility; D013109:Sphingomyelins / Q000737:chemistry / Q000378:metabolism
D000975:Antioxidants; D008074:Lipoproteins; D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D010713:Phosphatidylcholines; D013109:Sphingomyelins; D007052:Ibuprofen