N2,N4,N6-tri(hydroxymethyl)-N2,N4,N6-trimethylmelamine (trimelamol) is an efficient DNA cross-linking agent in vitro

Jackson, C.A., Hartley, J.A., Jenkins, T.C., Godfrey, R., Saunders, R. and Thurston, D.E. (1991) N2,N4,N6-tri(hydroxymethyl)-N2,N4,N6-trimethylmelamine (trimelamol) is an efficient DNA cross-linking agent in vitro. Biochemical Pharmacology, 42 (11). pp. 2091-2097. 10.1016/0006-2952(91)90343-4.

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DOI: 10.1016/0006-2952(91)90343-4

Abstract

An investigation of the mechanism of action of the antitumour agent trimelamol has established that it is an efficient interstrand DNA cross-linker in vitro, comparable to nitrogen mustards such as melphalan. Studies have shown that the cross-linking reaction is acid-catalysed but, unlike the nitrogen mustards, only partially reversible after treatment with piperidine. The bisalkylation (cross-linking) reaction appears to be concerted, and no 'second arm' reaction has been detected. The results of thermal denaturation studies are consistent with general DNA binding, and suggest a preference for GC-rich sites. The acid-catalysed reaction of trimelamol with a model nucleophile (thiophenol) has also been investigated and an adduct resulting from displacement of the three carbinolamine functions has been isolated and characterized.

Item Type:Article
Departments, units and centres:Department of Pharmaceutical and Biological Chemistry > Department of Pharmaceutical and Biological Chemistry
ID Code:2936
Journal or Publication Title:Biochemical Pharmacology
Deposited By:Library Staff
Deposited On:09 Mar 2012 14:11
Last Modified:09 Mar 2012 14:11

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