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.
Keywords: Alkylguanine, pseudosubstrates
Mini-Reviews in Medicinal Chemistry
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.
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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
DOI https://dx.doi.org/10.2174/1389557033487980 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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