A versatile strategy for the design and synthesis of novel ADP conjugates and their evaluation as potential poly(ADP-ribose) polymerase 1 inhibitors

作者：Sherstyuk Yuliya V; Zakharenko Alexandra L; Kutuzov Mikhail M; Chalova Polina V; Sukhanova Maria V; Lavrik Olga I; Silnikov Vladimir N; Abramova Tatyana V^*

来源：Molecular Diversity, 2017, 21(1): 101-113.

DOI：10.1007/s11030-016-9703-x

• Pyrophosphate synthesis
• PARP-1
• NAD(+) analogues
• PARP inhibitors

A versatile strategy for the synthesis of mimetics was developed, involving an efficient pyrophosphate linkage formation in key conjugates containing a functional amino group which acts as useful reactive anchor for further derivatization. These mimetics consist of ADP conjugated through a diphosphate chain to an extended aliphatic linker bearing an aromatic acid residue. A number of conjugates containing aromatic carboxylic acids were found to inhibit poly(ADP-ribose) synthesis catalyzed by poly(ADP-ribose) polymerase-1 (PARP-1). A new class of potential PARP-1 inhibitors mimicking , a substrate in the PARP-1 catalyzed reaction, was proposed.
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• 出版日期2017-2