Synthesis And Preliminary Application Of Biotinylated Adriamycin And Paclitaxel

The pharmaceutical explaination of anti-cancer drugs involves targets identification.In order to find the targets of different drugs,the probe remained previous biological activity was designed and obtained in rICent years.Our research based on ADM and PTX,which were ultilized as the first-line clinical anticancer drugs,by connICting ADM and PTX with biotin-aminohexanoic structure separately then interacted with streptavidin beads,we established a universal tool: biotinylated probe,which then be used in targets protein finding in MCF-7 residence cells.Results were listed as follow:1.Designed the sturucture of the biotinylated probe: biotin-C6-drug through computer and software tIChnique;Chosen one-step method to synthesize biotin-aminohexanoic(structure was verified by NMR,purity was 94.65%);Synthesized biotinylated ADM and biotinylated PTX with DCC-DMAP catalysis method,the structure of the products and the purity were confirmed by HNMR and HPLC.Tested inhibition and distribution of the biotinylated probe in vitro compared with original drug: The IC50 value of MCF-7/W cell was 8.554 ?M for biotinylated ADM and 8.656 ?M for ADM,and the IC50 value of MCF-7/ADM cell was 127.2 ?M for biotinylated ADM and 104.5 ?M for ADM;The IC50 value of MCF-7/W cell was 10.17 ?M for biotinylated PTX and 12.01 ?M for PTX,and the IC50 value of MCF-7/PTX cell was 82.16 ?M for biotinylated PTX and 93.26 ?M for PTX;Laser scanning confocal microscope(LSCM)also proved the biotinylated probe displayed the same distribution in cells compared with the original drug.2.Biotinylated ADM and biotinylated PTX were used as tools to investigate the different targets of ADM and PTX separately,based on the materials of MCF-7/ADM and MCF-7/PTX cell lysis buffer then tested by SDS-PAGE and Q TOF-MS,Junction plakoglobin and Hyaluronidase were found as the targets of ADM,Glutathione S-transferase P,Peroxiredoxin-1 and more than twenty kinds of protein were found as the targets of PTX,these targets were considered as effICtiveness in multidrug residence research.A viable method in finding and analyzing drug-protein targets was established in this paper.We provided a new feasible tool in targets protein identification research and make contribution to the development of new drug discovery and MDR research.