Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines.
Biosynthesis, synthesis, and biological activities of pyrrolobenzodiazepines.
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DOI：
10.1002/med.20212
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发表时间：
2012-03
影响因子：
13.3
通讯作者：
Gerratana, Barbara
中科院分区：
文献类型：
--
作者：
Gerratana, Barbara
关键词：
吡咯并苯并二氮杂卓（PBDs）是一类具有序列选择性的DNA烷基化试剂，具有显著的DNA烷基化活性.它们由放线菌自然产生或合成产生。天然产生的PBD的显著的广谱活性促进了几种PBD的合成，包括二聚体和杂合PBD，从而提高了DNA结合序列特异性和这类化合物的效力。然而，化学合成的限制阻止了最有效的PBD之一，西比罗霉素，一种天然产生的糖基化PBD的测试。直到最近，PBD的生物合成基因簇才被鉴定，这为通过突变合成和生物合成工程生产糖基化PBD打开了大门。本文综述了近年来天然产物吡咯并苯并二氮杂卓类化合物的生物合成研究进展。此外，它提供了一个概述的天然产生的PBDs的分离和表征，PBDs的化学合成，对DNA烷基化的机制，和DNA结合亲和力和细胞毒性性质的天然产生的和合成的吡咯并苯并二氮杂卓。
Pyrrolobenzodiazepines (PBDs) are sequence selective DNA alkylating agents with remarkable antineoplastic activity. They are either naturally produced by actinomycetes or synthetically produced. The remarkable broad spectrum of activities of the naturally produced PBDs encouraged the synthesis of several PBDs, including dimeric and hybrid PBDs yielding to an improvement in the DNA binding sequence specificity and in the potency of this class of compounds. However, limitation in the chemical synthesis prevented the testing of one of the most potent PBDs, sibiromycin, a naturally produced glycosylated PBDs. Only recently the biosynthetic gene clusters for PBDs have been identified opening the doors to the production of glycosylated PBDs by mutasynthesis and biosynthetic engineering. The present review describes the recent studies on the biosynthesis of naturally produced pyrrolobenzodiazepines. In addition, it provides an overview on the isolation and characterization of naturally produced PBDs, on the chemical synthesis of PBDs, on the mechanism of DNA alkylation, and on the DNA binding affinity and cytotoxic properties of both naturally produced and synthetic pyrrolobenzodiazepines.
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影响因子：
1.3
作者：
Baraldi, PG;Cacciari, B;Gambari, R
通讯作者：
Gambari, R
影响因子：
2.9
作者：
BARKLEY, MD;CHEATHAM, S;HURLEY, LH
通讯作者：
HURLEY, LH
影响因子：
5.7
作者：
Arnould, Stephanie;Spanswick, Victoria J.;Guichard, Sylvie M.
通讯作者：
Guichard, Sylvie M.
影响因子：
15
作者：
BOYD, FL;CHEATHAM, SF;HURLEY, LH
通讯作者：
HURLEY, LH
影响因子：
15
作者：
BRAHME, NM;GONZALEZ, JE;HURLEY, LH
通讯作者：
HURLEY, LH