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DNA-Targeted Inhibition of MGMT


Marsoner, Theodor; Schmidt, Olivia P; Triemer, Therese; Luedtke, Nathan W (2017). DNA-Targeted Inhibition of MGMT. Chembiochem, 18(10):894-898.

Abstract

The cationic porphyrin 5,10,15,20-tetrakis (diisopropyl-guanidine)-21H,23H-porphine (DIGPor) selectively binds to DNA containing O6 -methylguanine (O6 -MeG) and inhibits the DNA repair enzyme O6 -methylguanine-DNA methyltransferase (MGMT). The O6 -MeG selectivity and MGMT inhibitory activity of DIGPor were improved by incorporating ZnII into the porphyrin. The resulting metal complex (Zn-DIGPor) potentiated the activity of the DNA-alkylating drug temozolomide in an MGMT-expressing cell line. To the best of our knowledge, this is the first example of DNA-targeted MGMT inhibition.

Abstract

The cationic porphyrin 5,10,15,20-tetrakis (diisopropyl-guanidine)-21H,23H-porphine (DIGPor) selectively binds to DNA containing O6 -methylguanine (O6 -MeG) and inhibits the DNA repair enzyme O6 -methylguanine-DNA methyltransferase (MGMT). The O6 -MeG selectivity and MGMT inhibitory activity of DIGPor were improved by incorporating ZnII into the porphyrin. The resulting metal complex (Zn-DIGPor) potentiated the activity of the DNA-alkylating drug temozolomide in an MGMT-expressing cell line. To the best of our knowledge, this is the first example of DNA-targeted MGMT inhibition.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Uncontrolled Keywords:Organic Chemistry, Molecular Medicine, Biochemistry, Molecular Biology
Language:English
Date:2017
Deposited On:12 Jun 2018 13:11
Last Modified:23 Sep 2018 06:15
Publisher:Wiley-VCH Verlag
ISSN:1439-4227
OA Status:Closed
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1002/cbic.201600652
PubMed ID:28177192
Project Information:
  • : FunderSNSF
  • : Grant ID205320_165949
  • : Project TitleLive-cell imaging of DNA conformation and metabolism

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