顺二氨二水合铂(Ⅱ)与生物膜磷脂反应的核磁共振研究

A NMR Study of the Reaction Between cis-Diaquodiammine-platinum(Ⅱ) and Biomembranic Phospholipids

用NMR法研究了顺二氨二水合铂(Ⅱ)(AAP)与α-二棕搁酸磷脂酰胆碱(DPPC)的相互作用方式,以阐明在顺铂-细胞相互作用中膜磷脂的贡献。~1H及^(13)C谱表明,DPPC与AAP在CDCl_3中作用时,铂结合在DPPC的头部并引起DPPC分子中gauche向trans的构象转变。65℃测定DPPC脂质体与AAP在D_2O溶液中反应不同时间后的—(CH_3)_3、CH_a及—CH_3基团~1H的T_1值表明,铂在磷脂上的结合引起的磷脂构象变化会导致膜分子重新装配。

By means of NMR method, the modes and effects of the interaction between cis-diaquodiammineplatinum(Ⅱ) (AAP) and α-dipalmitoylglycerylphosphatidylcholine (DPPC) were studied to clarify the contribution of phospholipid-platinum reaction to the cisplatin-cell interactions. 1H and 13C spectra show that in CDCl3, as the result of DPPC-AAP reaction, the platinum binds to the head group of DPPC and induced a gauche to trans transformation in the glycerol moiety. The 1H T1 values of -N(CH3)3+, -(CH2)n- and -CH3 of DPPC in liposome form were determined at 65℃after the reaction with AAP in D2O for different time. The results indicate that the conformational change of phospholipid molecules and the changes in the set-up of the membranic molecules induced by the platinum binding may contribute to the cisplatin-cell interaction and are relevant to the anticancer activity and toxicity of cisplatin.