Site-specific PEGylation of lidamycin and its antitumor activity  

作　　者：Liang Li Boyang Shang Lei Hu Rongguang Shao Yongsu Zhen 

机构地区：[1]Institute of Medicinal Biotechnology,Chinese Academy of Medical Sciences & Peking Union Medical College

出　　处：《Acta Pharmaceutica Sinica B》2015年第3期264-269,共6页药学学报（英文版）

基　　金：supported by the National Science and Technology Major Project for Major New Drug Innovation (Nos.2013ZX09102064 and 2014ZX09201042-003)

摘　　要：In this study,N-terminal site-specific mono-PEGylation of the recombinant lidamycin apoprotein(r LDP) of lidamycin(LDM) was prepared using a polyethyleneglycol(PEG) derivative(Mw20 k Da) through a reactive terminal aldehyde group under weak acidic conditions(p H 5.5).The biochemical properties of m PEG-r LDP-AE,an enediyne-integrated conjugate,were analyzed by SDSPAGE,RP-HPLC,SEC-HPLC and MALDI-TOF.Meanwhile,in vitro and in vivo antitumor activity of m PEG-r LDP-AE was evaluated by MTT assays and in xenograft model.The results indicated that m PEGr LDP-AE showed significant antitumor activity both in vitro and in vivo.After PEGylation,m PEG-r LDP still retained the binding capability to the enediyne AE and presented the physicochemical characteristics similar to that of native LDP.It is of interest that the PEGylation did not diminish the antitumor efficacy of LDM,implying the possibility that this derivative may function as a payload to deliver novel tumortargeted drugs.In this study. N-tenninal site-specific mono-PEGylation of the recombinant lidamycin apoprotein (rLDP) of lidamycin (LDM) was prepared using a polyethyleneglycol (PEG) derivative (M-w 20 kDa) through a reactive, terminal aldehyde group under weak acidic conditions (pH 5.5). The biochemical properties of mPEG-iLDP-AE, an enediyne-integrated conjugate, were analyzed by SDS-PAGE, RP-HPLC, SEC-HPLC and MALDLTOF. Meanwhile, in vitro and in vivo antitumor activity of inPEG-rLDP-AE was evaluated by MTT assays and in xenograft model. The results indicated that mPEG-rLDP showed significant antitumor activity both in vitro and in vivo. After PEGylation, mPEG-rLDP still retained the binding capability to the enediyne AE and presented the physicochemical characteristics similar to that of native LDP. It is of interest that the PEGylation did not diminish the antitumor efficacy of LDM, implying the possibility that this derivative may function as a payload to deliver novel tumor targeted drugs. (C) 2015 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.

关 键 词：Enediyne antibiotic Polyethylene glycol Site-specific PEGylation LIDAMYCIN 

分 类 号：R943[医药卫生—药剂学]