Synthesis of New Alkylated Mononucleotide Analogues and Their Repair Proficiency by the Prokaryotic DNA Repair Protein AlkB

Abstract

We describe the synthesis of a variety of new alkylated mononucleotides and examine their repair proficiency with the prokaryotic direct DNA repair protein AlkB. A comparison of rates of repair among the different substrates supports the currently accepted radical mechanism.

Key words

bioorganic chemistry - dioxygenase - nucleotides - DNA damage - DNA repair

• References and Notes

• 1 Present address: Biozentrum, University of Basel, Klingelbergstrasse 50/70, 4056 Basel, Switzerland.
• 2a Bernstein BE, Meissner A, Lander ES. Cell 2007; 128: 669
• 2b Schwartz S, Agarwala Sudeep D, Mumbach Maxwell R, Jovanovic M, Mertins P, Shishkin A, Tabach Y, Mikkelsen Tarjei S, Satija R, Ruvkun G, Carr Steven A, Lander Eric S, Fink Gerald R, Regev A. Cell 2013; 155: 1409
• 3 Friedberg EC, Walker GC, Siede W, Wood RD. DNA Repair and Mutagenesis. American Society for Microbiology Press; Washington DC: 2005
• 4 Schärer OD. Angew. Chem. Int. Ed. 2003; 42: 2946
• 5a Mishina Y, Duguid E, He C. Chem. Rev. 2006; 106: 215
• 5b Zheng GQ, Fu Y, He C. Chem. Rev. 2014; 114: 4602
• 6 Delaney JC, Essigmann JM. Proc. Natl. Acad. Sci. U.S.A. 2004; 101: 14051
• 7 Li D, Fedeles BI, Shrivastav N, Delaney JC, Yang X, Wong C, Drennan CL, Essigmann JM. Chem. Res. Toxicol. 2013; 26: 1182
• 8 Maciejewska AM, Ruszel KP, Nieminuszczy J, Lewicka J, Sokołowska B, Grzesiuk E, Kuśmierek JT. Mutat. Res. 2010; 684: 24
• 9 Koivisto P, Duncan T, Lindahl T, Sedgwick B. J. Biol. Chem. 2003; 278: 44348
• 10 Trewick S, Henshaw T, Hausinger R, Lindahl T, Sedgwick B. Nature (London, U.K.) 2002; 419: 174
• 11 Duncan T, Trewick S, Koivisto P, Bates P, Lindahl T, Sedgwick B. Proc. Natl. Acad. Sci. U.S.A. 2002; 99: 16660
• 12 Ottria R, Casati S, Manzocchi A, Baldoli E, Mariotti M, Maier JA. M, Ciuffreda P. Bioorg. Med. Chem. 2010; 18: 4249
• 13 Jones JW, Robins RK. J. Am. Chem. Soc. 1963; 85: 193