Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads.

ABSTRACT: The value of small molecules that chemically modify proteins is increasingly being recognised and utilised in both chemical biology and drug discovery. The discovery of such chemical tools may be enabled by screening diverse sets of reactive probes. Most existing sets of reactive probes are armed with cysteine-directed warheads, a limitation that we sought to address. A connective synthesis was developed in which α-diazoamide substrates, armed with a S(VI) warhead, were reacted with diverse co-substrates. A high-throughput approach was used to identify promising substrate/co-substrate/catalyst combinations which were then prioritised for purification by mass-directed HPLC to yield a total of thirty reactive probes. The structural diversity of the probe set was increased by the multiplicity

SUBMITTER: Rice S 

PROVIDER: S-EPMC12456075 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature