标题:Enzymatic rhamnosylation of anticancer drugs by an alpha-l-rhamnosidase from Alternaria sp. L1 for cancer-targeting and enzyme-activated prodrug therapy
作者:Xu, Li; Liu, Xiaohong; Li, Yinping; Yin, Zhenhao; Jin, Lan; Lu, Lili; Qu, Jingyao; Xiao, Min
作者机构:[Xu, Li; Li, Yinping; Jin, Lan; Lu, Lili; Xiao, Min] Shandong Univ, Shandong Prov Key Lab Carbohydrate Chem & Glycobi, Natl Glycoengn Res Ctr, Qingdao 更多
通讯作者:Xiao, M;Xiao, M;Xiao, Min
通讯作者地址:[Xiao, M]Shandong Univ, Shandong Prov Key Lab Carbohydrate Chem & Glycobi, Natl Glycoengn Res Ctr, Qingdao 266237, Shandong, Peoples R China;[Xiao, M] 更多
来源:APPLIED MICROBIOLOGY AND BIOTECHNOLOGY
出版年:2019
卷:103
期:19
页码:7997-8008
DOI:10.1007/s00253-019-10011-0
关键词:Rhamnosylation; alpha-l-Rhamnosidase; Alternaria sp; L1;; Cancer-targeting; Prodrug
摘要:The synthesis of rhamnosylated compounds has gained great importance since these compounds have potential therapeutic applications. The enzymatic approaches for glycosylation of bioactive molecules have been well developed; however, the enzymatic rhamnosylation has been largely hindered by lacking of the glycosyl donor for rhamnosyltransferases. Here, we employed an alpha-l-rhamnosidase from Alternaria sp. L1 (RhaL1) to perform one-step rhamnosylation of anticancer drugs, including 2 '-deoxy-5-fluorouridine (FUDR), cytosine arabinoside (Ara C), and hydroxyurea (Hydrea). The key synthesis conditions including substrate concentrations and reaction time were carefully optimized, and the maximum yields of each rhamnosylated drugs were 57.7 mmol for rhamnosylated Ara C, 68.6 mmol for rhamnosylated Hydrea, and 42.2 mmol for rhamnosylated FUDR. It is worth pointing out that these rhamnosylated drugs exhibit little cytotoxic effects on cancer cells, but could efficiently restore cytotoxic activity when incubated with exogenous alpha-l-rhamnosidase, suggesting their potential applications in the enzyme-activated prodrug system. To evaluate the cancer-targeting ability of rhamnose moiety, the rhamnose-conjugated fluorescence dye rhodamine B (Rha-RhB) was constructed. The fluorescence probe Rha-RhB displayed much higher cell affinity and cellular internalization rate of oral cancer cell KB and breast cancer cell MDA-MB-231 than that of the normal epithelial cells MCF 10A, suggesting that the rhamnose moiety could mediate the specific internalization of rhamnosylated compounds into cancer cells, which greatly facilitated their applications for cancer-targeting drug delivery.
收录类别:EI;SCOPUS;SCIE
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070978772&doi=10.1007%2fs00253-019-10011-0&partnerID=40&md5=eab96d0cbd7af49fd1b3d0106236a135
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