Synthesis of oligodeoxyribonucleotides containing a conformationally-locked anti analogue of O6-methyl-2'-deoxyguanosine and their recognition by MGMT and Atl1.
We show that DNA containing a conformationally-locked anti analogue of O(6)-alkylguanine is a poor substrate for human O(6)-methylguanine-DNA methyltransferase (MGMT) and the alkyltransferase-like protein, Atl1. This highlights the requirement for the syn conformation and rationalises why certain O(6)-alkylguanines are poor MGMT substrates.
Centre for Chemical Biology, Department of Chemistry, Krebs Institute, University of Sheffield, Sheffield, S3 7HF, UK.
Kabir
K
Abdu
Miren K
MK
Aiertza
Oliver J
OJ
Wilkinson
Jane A
JA
Grasby
Pattama
P
Senthong
Andrew C
AC
Povey
Geoffrey P
GP
Margison
David M
DM
Williams
D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D018360:Crystallography, X-Ray; D006147:Guanine / Q000031:analogs & derivatives / Q000378:metabolism*; D006801:Humans; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism*; D009838:Oligodeoxyribonucleotides / Q000096:biosynthesis*; D011485:Protein Binding; D017434:Protein Structure, Tertiary
D009838:Oligodeoxyribonucleotides; D006147:Guanine; D019853:O(6)-Methylguanine-DNA Methyltransferase; D019883:Alkyl and Aryl Transferases