title: Selective Alkylation of C-Rich Bulge Motifs in Nucleic Acids by Quinone Methide Derivatives.
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 (Zn(2+) , Ni(2+) and Cd(2+) ). 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.
authors.affiliation: Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218 (USA). tuanlo@utu.fi.|Department of Chemistry, University of Turku, 20014 Turku (Finland). tuanlo@utu.fi.
authors.forename: Tuomas
authors.initials: T
authors.lastname: Lönnberg
authors.affiliation: Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218 (USA).
authors.forename: Mark
authors.initials: M
authors.lastname: Hutchinson
authors.affiliation: Department of Chemistry, Johns Hopkins University, Baltimore, Maryland 21218 (USA).
authors.forename: Steven
authors.initials: S
authors.lastname: Rokita
mesh_terms: D000478:Alkylation; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry*; D004586:Electrophoresis / Q000379:methods; D045563:Indolequinones / Q000737:chemistry*; D009696:Nucleic Acids / Q000032:analysis / Q000737:chemistry*; D009841:Oligonucleotides / Q000032:analysis / Q000737:chemistry*; D010084:Oxidation-Reduction
chemical_list: D018736:DNA Adducts; D045563:Indolequinones; D009696:Nucleic Acids; D009841:Oligonucleotides; C068040:quinone methide
keywords: alkylation; cyclen; metal chelate; nucleic acids; quinone methide