Selective Alkylation of C‐Rich Bulge Motifs in Nucleic Acids by Quinone Methide Derivatives |
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Authors: | Dr. Tuomas Lönnberg Mark Hutchinson Prof. Dr. Steven Rokita |
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Affiliation: | 1. Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218 (USA);2. Department of Chemistry, University of Turku, 20014 Turku (Finland) |
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Abstract: | A quinone methide precursor featuring a bis‐cyclen anchoring moiety has been synthesized and its capacity to alkylate oligonucleotide targets quantified in the presence and absence of divalent metal ions (Zn2+, Ni2+ and Cd2+). The oligonucleotides were designed for testing the sequence and secondary structure specificity of the reaction. Gel electrophoretic analysis revealed predominant alkylation of C‐rich bulges, regardless of the presence of divalent metal ions or even the bis‐cyclen anchor. This C‐selectivity appears to be an intrinsic property of the quinone methide electrophile as reflected by its reaction with an equimolar mixture of the 2′‐deoxynucleosides. Only dA‐N1 and dC‐N3 alkylation products were detected initially and only the dC adduct persisted for detection under conditions of the gel electrophoretic analysis. |
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Keywords: | alkylation cyclen metal chelate nucleic acids quinone methide |
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