2,5-Diketopiperazines: A New Class of Poly(ADP-ribose)polymerase Inhibitors
- Авторлар: Nilov D.1, Yashina K.2, Gushchina I.2, Zakharenko A.3, Sukhanova M.3, Lavrik O.3, Švedas V.1,2
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Мекемелер:
- Belozersky Institute of Physico-Chemical Biology
- Faculty of Bioengineering and Bioinformatics
- Institute of Chemical Biology and Fundamental Medicine
- Шығарылым: Том 83, № 2 (2018)
- Беттер: 152-158
- Бөлім: Article
- URL: https://journals.rcsi.science/0006-2979/article/view/151601
- DOI: https://doi.org/10.1134/S0006297918020074
- ID: 151601
Дәйексөз келтіру
Аннотация
We show for the first time that natural 2,5-diketopiperazines (cyclic dipeptides) can suppress the activity of the important anticancer target poly(ADP-ribose)polymerase (PARP). Cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) can interact with the key residues of the PARP-1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(L-Ala-L-Ala) and cyclo(L-Ala-D-Ala) forms hydrogen bonds with the Gly863 residue, while the second amide group can form a hydrogen bond with the catalytic residue Glu988, and the side chain can make a hydrophobic contact with Ala898. Newly identified diketopiperazine inhibitors are promising basic structures for the design of more effective inhibitors of PARP family enzymes. The piperazine core with two chiral centers provides many opportunities for structural optimization.
Авторлар туралы
D. Nilov
Belozersky Institute of Physico-Chemical Biology
Email: vytas@belozersky.msu.ru
Ресей, Moscow, 119991
K. Yashina
Faculty of Bioengineering and Bioinformatics
Email: vytas@belozersky.msu.ru
Ресей, Moscow, 119991
I. Gushchina
Faculty of Bioengineering and Bioinformatics
Email: vytas@belozersky.msu.ru
Ресей, Moscow, 119991
A. Zakharenko
Institute of Chemical Biology and Fundamental Medicine
Email: vytas@belozersky.msu.ru
Ресей, Novosibirsk, 630090
M. Sukhanova
Institute of Chemical Biology and Fundamental Medicine
Email: vytas@belozersky.msu.ru
Ресей, Novosibirsk, 630090
O. Lavrik
Institute of Chemical Biology and Fundamental Medicine
Email: vytas@belozersky.msu.ru
Ресей, Novosibirsk, 630090
V. Švedas
Belozersky Institute of Physico-Chemical Biology; Faculty of Bioengineering and Bioinformatics
Хат алмасуға жауапты Автор.
Email: vytas@belozersky.msu.ru
Ресей, Moscow, 119991; Moscow, 119991
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