Targeted Labeling of DNA by Methyltransferase-Directed Transfer of Activated Groups (mTAG)

Methyltransferases catalyze highly specific transfers of methyl groups from the ubiquitous cofactor <i>S</i>-adenosyl-l-methionine (AdoMet) to various biopolymers like DNA, RNA, and proteins. Here we describe the first synthetic analogue of AdoMet with an activated side chain carrying a primary amino group that permits efficient methyltransferase-directed functionalization of DNA and subsequent amine-specific chemoligations with various reporter groups. The demonstrated two-step sequence-specific labeling of natural DNA offers a facile way to query the methylation status of the target sites and envisions numerous applications in functional studies and medical diagnostics.