Biochemistry (Moscow)

, Volume 83, Issue 2, pp 152–158 | Cite as

2,5-Diketopiperazines: A New Class of Poly(ADP-ribose)polymerase Inhibitors

  • D. K. Nilov
  • K. I. Yashina
  • I. V. Gushchina
  • A. L. Zakharenko
  • M. V. Sukhanova
  • O. I. Lavrik
  • V. K. ŠvedasEmail author


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.


diketopiperazine piperazinedione poly(ADP-ribose)polymerase inhibitor molecular modeling docking molecular dynamics 

Abbreviation (biaoti)




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2,5-Diketopiperazines: A New Class of Poly(ADP-ribose)polymerase Inhibitors


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Copyright information

© Pleiades Publishing, Ltd. 2018

Authors and Affiliations

  • D. K. Nilov
    • 1
  • K. I. Yashina
    • 2
  • I. V. Gushchina
    • 2
  • A. L. Zakharenko
    • 3
  • M. V. Sukhanova
    • 3
  • O. I. Lavrik
    • 3
  • V. K. Švedas
    • 1
    • 2
    Email author
  1. 1.Belozersky Institute of Physico-Chemical BiologyLomonosov Moscow State UniversityMoscowRussia
  2. 2.Faculty of Bioengineering and BioinformaticsLomonosov Moscow State UniversityMoscowRussia
  3. 3.Institute of Chemical Biology and Fundamental MedicineSiberian Branch of the Russian Academy of SciencesNovosibirskRussia

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