Inhibition of Poly(ADP-Ribose) Polymerase by Nucleic Acid Metabolite 7-Methylguanine

Content Provider	Semantic Scholar
Author	Tararov, Vitali I. Mikhailov, Sergey N.
Copyright Year	2016
Abstract	The ability of 7-methylguanine, a nucleic acid metabolite, to inhibit poly(ADP-ribose)polymerase-1 (PARP-1) and poly(ADP-ribose)polymerase-2 (PARP-2) has been identified in silico and studied experimentally. The amino group at position 2 and the methyl group at position 7 were shown to be important substituents for the efficient binding of purine derivatives to PARPs. The activity of both tested enzymes, PARP-1 and PARP-2, was suppressed by 7-methylguanine with IC50 values of 150 and 50 μM, respectively. At the PARP inhibitory concentration, 7-methylguanine itself was not cytotoxic, but it was able to accelerate apoptotic death of BRCA1-deficient breast cancer cells induced by cisplatin and doxorubicin, the widely used DNA-damaging chemotherapeutic agents. 7-Methylguanine possesses attractive predictable pharmacokinetics and an adverse-effect profile and may be considered as a new additive to chemotherapeutic treatment.
Starting Page	108
Ending Page	115
Page Count	8
File Format	PDF HTM / HTML
Alternate Webpage(s)	http://pubmedcentralcanada.ca/pmcc/articles/PMC4947994/pdf/AN20758251-29-108.pdf
PubMed reference number	27437145v1
Volume Number	8
Journal	Acta naturae
Language	English
Access Restriction	Open
Subject Keyword	7-methylguanine Adenosine Diphosphate Cisplatin Doxorubicin Inhibitory Concentration 50 Mammary Neoplasms Methyl Group Nucleic Acids PARP1 protein, human Poly(ADP-ribose) Polymerases Purines Ribose cancer cell
Content Type	Text
Resource Type	Article