Prodrugs of dynemicin analogs for selective chemotherapy mediated by an aldolase catalytic Ab

被引：25
作者：
Sinha, SC
Li, LS
Miller, GP
Dutta, S
Rader, C
Lerner, RA
机构：
[1] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA
[2] Scripps Res Inst, Dept Mol Biol, La Jolla, CA 92037 USA
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2004年 / 101卷 / 09期
关键词：
D O I：
10.1073/pnas.0307319101
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Prodrugs of dynemicin analogs were synthesized, and their activation by aldolase antibody (Ab) 38C2 was evaluated by DNA-cleaving activity, as well as tumor cell growth inhibition. Further, we provide evidence that the activated enediynes underwent covalent crosscoupling with the aldolase Ab, which appears to be a limiting factor of their tumor cell growth-inhibiting activity and should be of general interest in the field of enediyne chemotherapy. These findings might open new avenues for defined conjugations of small molecule drugs to mAbs in general and aldolase Abs in particular.
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页码：3095 / 3099
页数：5
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