# Dual Stabilization of S‑Adenosylmethionine for Enzymatic DNA Labeling

## TL;DR

Researchers developed more stable versions of a key molecule used for labeling DNA, improving its effectiveness in biochemical experiments.

## Contribution

A new class of stabilized AdoMet analogues with a conformationally constrained proline side chain and selenonium modification is introduced.

## Key findings

- The new analogues show up to a 90-fold increase in half-life compared to AdoMet.
- They retain activity with DNA methyltransferases and enable sequence-specific DNA labeling.
- Both two- and single-step labeling approaches with fluorescent dyes are effective using these analogues.

## Abstract

S-Adenosyl-l-methionine (AdoMet)
analogues
are a powerful tool for site-specific biomolecular labeling via methyltransferase
(MTase)-catalyzed transfer reactions. However, their utility is often
limited by their poor chemical stability under enzymatic reaction
conditions. Here, we report a new class of stabilized AdoMet analogues,
featuring a conformationally constrained proline side chain in place
of homoalanine. This substitution inhibits intramolecular cyclization,
which is a major decomposition pathway. Combination with selenonium
modification, which suppresses depurination, yields analogues with
up to a 90-fold increase in half-life relative to AdoMet. These cofactors
retain activity with DNA MTases and allow sequence-specific labeling
of plasmid DNA using both two- and single-step approaches with fluorescent
dyes.