Generic placeholder image

Mini-Reviews in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

O6-Alkylguanine-DNA Alkyltransferase Inactivation in Cancer Chemotherapy

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

Volume 3, Issue 5, 2003

Page: [471 - 485] Pages: 15

DOI: 10.2174/1389557033487980

Price: $65

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


Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy