Synthesis of a series of NAD+ analogues, potential inhibitors of PARP 1, using ADP conjugates functionalized at the terminal phosphate group

Yu V. Sherstyuk, A. L. Zakharenko, M. M. Kutuzov, M. V. Sukhanova, O. I. Lavrik, V. N. Silnikov, T. V. Abramova

Результат исследования: Научные публикации в периодических изданияхстатья

4 Цитирования (Scopus)

Аннотация

A convenient approach has been proposed to the synthesis of nicotinamide adenine dinucleotide (NAD+) mimetics, which comprise morpholino analogues of nucleosides. The approach is based on the use of ADP conjugates containing an amino group, which is tethered to the terminal phosphate through the aliphatic linker by the phosphodiester bond. We have synthesized four series of the NAD+ mimetics, which differ in the type of the modified nucleoside (2-aminomethylmorpholine (Mor) or 2-aminomethyl-4-carboxymethylmorpholine (MorGly) derivatives), in the linker length, and in the manner of the nucleoside attachment to the ADP derivative. We have studied the efficiency of NAD+ mimetics in the inhibition of the auto-poly(ADP-ribosyl)ation by the PARP 1 enzyme. The linker length, the mode of the attachment of the morpholino nucleoside analogue, and the nature of the heterocyclic base of the modified nucleoside were shown to inf luence the inhibition efficiency.

Язык оригиналаанглийский
Страницы (с-по)76-83
Число страниц8
ЖурналRussian Journal of Bioorganic Chemistry
Том43
Номер выпуска1
DOI
СостояниеОпубликовано - 1 янв 2017

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