Title
DNA-Targeted Inhibition of MGMT
Author
Nathan William Luedtke, Theodor Marsoner, Olivia Schmidt, Therese Trimer
Year
2017
Journal
ChemBioChem
Abstract
The cationic porphyrin 5,10,15,20-tetrakis (diisopropylguanidine)-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 was 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, these results provide the first examples of DNAtargeted MGMT inhibition.
Instrument
J-715
Keywords
Circular dichroism, DNA structure, Ligand binding, Biochemistry