Spectroscopic and electrochemical studies on molecular recognition of tetrathiafulvalene derivative with P-glycoprotein and drug-resistant leukemia cells  

作　　者：Yuanyuan Zhang Changyu Wu Hui Jiang Jinglin Zuo Xuemei Wang 

机构地区：[1]State Key Laboratory of Bioelectronics (Chien-Shiung Wu Laboratory) [2]Southeast University [3]State Key Laboratory of Coordination Chemistry [4]School of Chemistry and Chemical Engineering,Nanjing University

出　　处：《Science China Chemistry》2015年第7期1193-1199,共7页中国科学（化学英文版）

基　　金：supported by the National Natural Science Foundation of China(81325011);the National High Technology Research&Development Program of China(2012AA022703);the National Basic Research Program of China(2010CB732404);the Major Science&Technology Project of Suzhou(ZXY2012028)

摘　　要：Cancer is still one of the important diseases that threatens the health of people. Multidrug resistance(MDR) is the main factor that leads to the failure of cancer chemotherapy. Thus, MDR diagnosis could facilitate the monitoring of the therapy process and realization of efficient treatment of tumors. In this study, we have tried to use a new tetrathiafulvalene(TTF) derivative(TTF-(COONBu4)2) to sensitively recognize the MDR through the multi-signal responsive strategy. The relevant electrochemical and spectroscopic studies demonstrate the specific binding behavior of TTF-(COONBu4)2 with P-glycoprotein(P-gp) as well as drug-resistant leukemia cells. Especially due to the over-expression of specific components of P-gp on the plasma membranes of drug resistant cells, the electrochemical and hydrophilic/hydrophobic features of drug resistant-leukemia cells are apparently different from those of other kinds of leukemia cells. Meanwhile, Fourier transform infrared spectroscopic study illustrates that the most intense vibration band of TTF moieties in the 1400–1600 cm-1 range is almost smeared out upon binding to P-gp, and the binding of TTF-(COONBu4)2 to P-gp may also lead to changes in protein secondary structure and backbone. This observation may advance the development of the new TTF agent for the promising clinical diagnosis and monitoring of MDR of tumors with the aim of successful chemotherapy for human cancer.Cancer is still one of the important diseases that threatens the health of people. Multidrug resistance （MDR） is the main factor that leads to the failure of cancer chemotherapy. Thus, MDR diagnosis could facilitate the monitoring of the therapy process and realization of efficient treatment of tumors. In this study, we have tried to use a new tetrathiafulvalene （TTF） derivative （TTF-（COONBu4）2） to sensitively recognize the MDR through the multi-signal responsive strategy. The relevant electrochem- ical and spectroscopic studies demonstrate the specific binding behavior of TTF-（COONBu4）2 with P-glycoprotein （P-gp） as well as drug-resistant leukemia cells. Especially due to the over-expression of specific components of P-gp on the plasma membranes of drug resistant cells, the electrochemical and hydrophilic/hydrophobic features of drug resistant-leukemia cells are apparently different from those of other kinds of leukemia cells. Meanwhile, Fourier transform infrared spectroscopic study illustrates that the most intense vibration band of TTF moieties in the 1400-1600 cm-1 range is almost smeared out upon bind- ing to P-gp, and the binding of TTF-（COONBu4）2 to P-gp may also lead to changes in protein secondary structure and back- bone. This observation may advance the development of the new TTF agent for the promising clinical diagnosis and monitor- ing of MDR of tumors with the aim of successful chemotherapy for human cancer.

关 键 词：tetrathiafulvalene derivative leukemia cell P-GLYCOPROTEIN electrochemical detection Fourier transform infraredspectroscopy 

分 类 号：R730.43[医药卫生—肿瘤] O657[医药卫生—临床医学]