Substituted O6-benzylguanine derivatives and their inactivation of human O6-alkylguanine-DNA alkyltransferase.
Several new O6-benzylguanine analogs bearing increasingly bulky substituent groups on the benzene ring or at position 9 were tested for their ability to inactivate the human DNA repair protein, O6-alkylguanine-DNA alkyltransferase. Substitution on the benzene ring was well tolerated although activity varied considerably with structural changes in groups attached to position 9. For this site, activity was preserved with large or small lipophilic groups while introduction of non-carbohydrate polar groups generally reduced activity regardless of their size.
Chae
M Y
MY
Chemistry of Carcinogenesis Laboratory, ABL-Basic Research Program, National Cancer Institute-Frederick Cancer Research and Development Center, Maryland 21702.
McDougall
M G
MG
Dolan
M E
ME
Swenn
K
K
Pegg
A E
AE
Moschel
R C
RC
D003110:Colonic Neoplasms / Q000201:enzymology; D006147:Guanine / Q000031:analogs & derivatives* / Q000737:chemistry; D006801:Humans; D008780:Methyltransferases / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D019853:O(6)-Methylguanine-DNA Methyltransferase; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
C064976:O(6)-benzylguanine; D006147:Guanine; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase