Sequence Specific Alkylation of DNA

The availability of sequence-specific DNA binding molecules led to the development of bifunctional polyamides that covalently react with the minor groove of DNA. Two classes of alkylating agents were conjugated to the hairpin turn unit and bound proximal to their alkylation sites by a DNA-binding polyamide [58, 59]. 

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WuRTZ, N.R. and P.B. Dervan. Sequence-specific alkylation of DNA by hairpin pyrrole-imidazole polyamide conjugates. Chem. Biol. 2000, 7, 153-161. 

Non-sequence-specific or global DNA damage is generally caused by random DNA alkylation, cross-linking or strand scission, the mechanisms and consequences of which have been previously mentioned. 

Schulz, W. G. Nieman, R. A. Skibo, E. B. Evidence for DNA phosphate backbone alkylation and cleavage by pyrrolo[l,2-a] benzimidazoles, small molecules capable of causing sequence specific phosphodiester bond hydrolysis. Proc. Natl. Acad. Sci. USA 1995, 92, 11854-11858. 

Prakash, A. S. Denny, W. A. Gourdie, T. A. Valu, K. K. Woodgate, P. D. Wakelin, L. P. G. DNA-directed alkylating ligands as potential antitumor agents sequence specificity of alkylation by intercalating aniline mustards. Biochemistry 1990, 29, 9799-9807. 

Premaratne, S., Mandel, M. Mower, H.F. (1995) Detection of mutagen specific adduct formation in DNA using sequencing methodology. Int. J. Biochem. Cell Biol., 27, 789-794 Quintero-Ruiz, A., Paz-Neri, L.L. Villa-Trevino, S. (1981) Indirect alkylation of CBA mouse... 

Synthesis and biological properties of sequence-specific DNA-alkylating pyrrole-imidazole polyamides 06ACR935. 

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