Direct Assembly of a Fully Functionalized-Fragment Library for Photoaffinity Labeling Applications via Mild A³‑Coupling in Water.
- 1Institute of Applied Synthetic Chemistry, TU Wien, Getreidemarkt 9, 1060 Vienna, Austria.
- 2Solgate GmbH, IST Park, Plöcking 1, 3400 Klosterneuburg, Austria.
Abstract
In classical photoaffinity labeling (PAL) probes, diazirine and alkyne handles are attached via a flexible spacer, which inherently modulates biological activity. We herein report a diazirine-tolerant A³-coupling (aldehyde-amine-alkyne) catalyzed by AuCl₃ in water at room temperature, enabling direct assembly of fully functionalized fragments (FFFs) with rigidly positioned cross-linking and retrieval tags. This mild protocol accommodates diverse aldehydes endowed with benzenes or aliphatic systems, and so far underdeveloped heteroaromatic moieties such as pyridines, quinolines, and indoles, thus delivering FFFs exhibiting more complex structural scaffolds, which are of interest in medicinal chemistry. Postfunctionalization via a mild Suzuki coupling demonstrates how chemical diversity can be further expanded. A library of over 60 compounds were accessed, establishing the methodology's broad scope. Furthermore, biological testing tentatively showed that these new probes exhibit reactivity with the proteome, enabling labeling in human cells.
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BibTeX
@article{bauhoff2026direct,
title = {{Direct Assembly of a Fully Functionalized-Fragment Library for Photoaffinity Labeling Applications via Mild A³‑Coupling in Water.}},
author = {Thomas Bauhoff and Andrea Federici and Andreas Gollner and Peter Gärtner and Nicolas Kratena},
journal = {ACS bio \& med chem Au},
year = {2026},
month = oct,
doi = {10.1021/acsbiomedchemau.6c00160},
url = {https://europepmc.org/article/MED/42921038},
note = {CC BY},
}
RIS
TY - JOUR
TI - Direct Assembly of a Fully Functionalized-Fragment Library for Photoaffinity Labeling Applications via Mild A³‑Coupling in Water.
AU - Thomas Bauhoff
AU - Andrea Federici
AU - Andreas Gollner
AU - Peter Gärtner
AU - Nicolas Kratena
PY - 2026
DA - 2026/10/05
JO - ACS bio & med chem Au
DO - 10.1021/acsbiomedchemau.6c00160
UR - https://europepmc.org/article/MED/42921038
AB - In classical photoaffinity labeling (PAL) probes, diazirine and alkyne handles are attached via a flexible spacer, which inherently modulates biological activity. We herein report a diazirine-tolerant A³-coupling (aldehyde-amine-alkyne) catalyzed by AuCl₃ in water at room temperature, enabling direct assembly of fully functionalized fragments (FFFs) with rigidly positioned cross-linking and retrieval tags. This mild protocol accommodates diverse aldehydes endowed with benzenes or aliphatic systems, and so far underdeveloped heteroaromatic moieties such as pyridines, quinolines, and indoles, thus delivering FFFs exhibiting more complex structural scaffolds, which are of interest in medicinal chemistry. Postfunctionalization via a mild Suzuki coupling demonstrates how chemical diversity can be further expanded. A library of over 60 compounds were accessed, establishing the methodology's broad scope. Furthermore, biological testing tentatively showed that these new probes exhibit reactivity with the proteome, enabling labeling in human cells.
SN - 2694-2437
ER -