Direct introduction of R-SO2F moieties into proteins and protein-polymer conjugation using SuFEx chemistry

SuFEx-enabled, agnostic discovery of covalent inhibitors of human neutrophil elastase

“…click chemistry | SuFEx | agnostic | covalent inhibitor | elastase S ulfur fluoride exchange (SuFEx)-the new-generation click chemistry, since first introduced in 2014 (1), has quickly found diverse applications across an array of fields (DOI: 10.1039/C8CS00960K), including chemical synthesis (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12), material science (13)(14)(15)(16)(17)(18)(19), chemical biology (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32), and drug discovery (33,34). SuFEx creates robust intermolecular links between modules.…”

“…In the context of selective in vitro or in vivo covalent capture of proteins by compounds containing a S-F bond that can undergo SuFEx reaction (i.e., SuFExable compounds), examples are rapidly accumulating (20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31). However, we are still far from making strong a priori inferences about the various factors that might relate to a given capture's occurrence.…”

Synthesis and Chemical Transformations of Fluorosulfates

“…A model reaction between bovine serum albumin (BSA) and a SO 2 F‐containing polyethylene glycol (PEG) was designed by the Averick group to demonstrate the feasibility of utilizing SuFEx chemistry in protein–polymer bioconjugation . Model polymer PEG−Bn−OSO 2 F was synthesized from a PEG−NHS ester ( M n =5000; NHS= N ‐hydroxysuccinimide).…”

SuFEx – a selectively triggered chemistry for fast, efficient and equimolar polymer–polymer coupling reactions

“…20 This "click" reaction has already demonstrated its potential in polycondensations, 21 side chain modifications, 22,23 and site specific binding for bioapplications. 24,25 Despite these beneficial properties and the selectivity of the reactive moieties, its application towards efficient polymer-polymer coupling has not yet been reported. To address this, we designed two suitable chain transfer agents (CTAs) bearing the respective functionalities for SuFEx and tested them in RAFT polymerizations as model radical processes.…”