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DNA‐Targeted Inhibition of MGMT
Author(s) -
Marsoner Theodor,
Schmidt Olivia P.,
Triemer Therese,
Luedtke Nathan W.
Publication year - 2017
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.201600652
Subject(s) - o 6 methylguanine dna methyltransferase , dna , methyltransferase , chemistry , dna methyltransferase , porphyrin , temozolomide , guanidine , dna repair , biochemistry , glioblastoma , cancer research , biology , methylation
The cationic porphyrin 5,10,15,20‐tetrakis (diisopropyl‐guanidine)‐21 H ,23 H ‐porphine (DIGPor) selectively binds to DNA containing O 6 ‐methylguanine ( O 6 ‐MeG) and inhibits the DNA repair enzyme O 6 ‐methylguanine‐DNA methyltransferase (MGMT). The O 6 ‐MeG selectivity and MGMT inhibitory activity of DIGPor were improved by incorporating Zn II 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.