O6-Alkylguanine-DNA Alkyltransferase Inactivation in Cancer Chemotherapy

Title: O6-Alkylguanine-DNA Alkyltransferase Inactivation in Cancer Chemotherapy

Volume: 3 Issue: 5

Author(s): R. S. McElhinney, T. B.H. McMurry and G. P. Margison

Affiliation:

Keywords: Alkylguanine, pseudosubstrates

Abstract: The protein O6-alkylguanine-DNA alkyltransferase is the basis of an important process for repairing damage to cellular DNA, which renders cells resistant to drugs that alkylate at the O6-position of guanine residues. The development of various pseudosubstrates which inactivate this protein is reviewed, from a chemical standpoint. Study of the influence of pseudosubstrate molecular structure on their interaction with the active site cysteine has progressed together with direct investigation of protein structure. Combination therapy using a powerful inactivator with a suitable alkylating agent shows great clinical promise in the treatment of cancer, particularly when some degree of selectivity is possible.

Cite this article as:

McElhinney S. R., McMurry B.H. T. and Margison P. G., O6-Alkylguanine-DNA Alkyltransferase Inactivation in Cancer Chemotherapy, Mini-Reviews in Medicinal Chemistry 2003; 3 (5) . https://dx.doi.org/10.2174/1389557033487980