Synthesis of oligodeoxyribonucleotides containing a conformationally-locked anti analogue of O6-methyl-2'-deoxyguanosine and their recognition by MGMT and Atl1

Chem Commun (Camb). 2012 Nov 25;48(91):11214-6. doi: 10.1039/c2cc36252j. Epub 2012 Oct 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkyl and Aryl Transferases / metabolism*
  • Crystallography, X-Ray
  • Guanine / analogs & derivatives
  • Guanine / metabolism*
  • Humans
  • O(6)-Methylguanine-DNA Methyltransferase / metabolism*
  • Oligodeoxyribonucleotides / biosynthesis*
  • Protein Binding
  • Protein Structure, Tertiary

Substances

  • Oligodeoxyribonucleotides
  • Guanine
  • O(6)-Methylguanine-DNA Methyltransferase
  • Alkyl and Aryl Transferases