What question did this study set out to answer?

The research aims to enhance the utility of S-Adenosylmethionine analogues for DNA labeling by improving their chemical stability.

March 14, 2026Open Access

Dual Stabilization of S -Adenosylmethionine for Enzymatic DNA Labeling

Key Points

The research aims to enhance the utility of S-Adenosylmethionine analogues for DNA labeling by improving their chemical stability.
Developed stabilized S-Adenosylmethionine analogues with a proline side chain
Tested analogues with methyltransferases for their labeling efficiency
Evaluated the chemical stability and half-life under enzymatic conditions
Achieved up to a 90-fold increase in half-life compared to AdoMet
Maintained activity with DNA methyltransferases
Facilitated sequence-specific labeling of plasmid DNA with fluorescent dyes

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.

Dual Stabilization of S -Adenosylmethionine for Enzymatic DNA Labeling

Key Points

Abstract

Cite This Study