2,5-Diketopiperazines: a new class of poly(ADP-ribose)polymerase InhibitorsстатьяПереводИсследовательская статья
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Дата последнего поиска статьи во внешних источниках: 20 марта 2018 г.
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 PARP1 active site, as demonstrated using docking and molecular dynamics simulations. One of the amide groups of cyclo(LAlaLAla) and cyclo(LAlaDAla) 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.