Fluorescent DNA Labeling by N‐Mustard Analogues of <i>S</i>‐Adenosyl‐<scp>L</scp>‐Methionine

Abstract

Azide and alkyne-functionalized N-mustard analogues of S-adenosyl-L-methionine have been synthesized and were demonstrated to undergo efficient methyltransferase-dependent DNA alkylation by M.TaqI and M.HhaI. Subsequent labeling of the DNA with a fluorophore was carried out using copper-catalyzed azide-alkyne cycloaddition chemistry and was visualized by fluorescence scanning. This work demonstrates the utility of functionalized N-mustard analogues as biochemical tools to study biological methylation and offers a facile way to site-selectively label substrates of DNA methyltransferases.