Fluorescent cAMP Analogs: Enzymatic Synthesis, Unexpected Photophysical Behavior and Protein Kinase A Recognition
Abstract
Cyclic adenosine monophosphate (cAMP) is a second messenger, regulating critical physiological processes. We report the enzymatic synthesis, unique photophysical features, and biological activity of novel emissive cAMP analogs (c th AMP and c tz AMP), comprised of thiopheno‐ and isothiazolo‐based families of isomorphic ribonucleotides. The unexpectedly high brightness of c th AMP compared to th ATP and th AMP, its precursor and hydrolysis products, respectively, driven by an anti ‐to‐ syn conformational shift upon cyclization, is employed for real‐time monitoring of the adenylyl cyclase (AC) mediated synthesis and phosphodiesterase (PDE) mediated hydrolysis. Importantly, these emissive analogs effectively activate protein kinase A (PKA). This study provides critical insights into the biomolecular recognition and catalytic mechanism of cAMP‐regulating enzymes, establishing these isomorphic analogs as potential tools for investigating cAMP‐dependent protein–ligand interaction through fluorescence spectroscopy.
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BibTeX
@article{cong2026fluorescent,
title = {{Fluorescent cAMP Analogs: Enzymatic Synthesis, Unexpected Photophysical Behavior and Protein Kinase A Recognition}},
author = {Deyuan Cong and Victor Dubois and Jamie Lam and Yitzhak Tor},
journal = {Angewandte Chemie International Edition},
year = {2026},
month = aug,
doi = {10.1002/anie.6334998},
url = {https://hal.science/hal-05746908v1},
note = {CC BY},
}
RIS
TY - JOUR
TI - Fluorescent cAMP Analogs: Enzymatic Synthesis, Unexpected Photophysical Behavior and Protein Kinase A Recognition
AU - Deyuan Cong
AU - Victor Dubois
AU - Jamie Lam
AU - Yitzhak Tor
PY - 2026
DA - 2026/08/07
JO - Angewandte Chemie International Edition
DO - 10.1002/anie.6334998
UR - https://hal.science/hal-05746908v1
AB - Cyclic adenosine monophosphate (cAMP) is a second messenger, regulating critical physiological processes. We report the enzymatic synthesis, unique photophysical features, and biological activity of novel emissive cAMP analogs (c th AMP and c tz AMP), comprised of thiopheno‐ and isothiazolo‐based families of isomorphic ribonucleotides. The unexpectedly high brightness of c th AMP compared to th ATP and th AMP, its precursor and hydrolysis products, respectively, driven by an anti ‐to‐ syn conformational shift upon cyclization, is employed for real‐time monitoring of the adenylyl cyclase (AC) mediated synthesis and phosphodiesterase (PDE) mediated hydrolysis. Importantly, these emissive analogs effectively activate protein kinase A (PKA). This study provides critical insights into the biomolecular recognition and catalytic mechanism of cAMP‐regulating enzymes, establishing these isomorphic analogs as potential tools for investigating cAMP‐dependent protein–ligand interaction through fluorescence spectroscopy.
SN - 1433-7851
SN - 1521-3773
ER -