98-62-4Relevant articles and documents
SuFExable Isocyanides for Ugi Reaction: Synthesis of Sulfonyl Fluoro Peptides
Xu, Shuheng,Cui, Sunliang
supporting information, p. 5197 - 5202 (2021/07/20)
Herein, the sulfonyl fluoro isocyanides were first developed as a new type of SuFExable synthon, and they are used as building blocks in the Ugi reaction (U-4CR). The Ugi reaction was established and the substrate scope was investigated, and various sulfonyl fluoro α-amino amides and peptides could be reached in a one-step synthesis. Therefore, this protocol opens a new vision for SuFExable building blocks and click chemistry, and it also provides a distinct approach to sulfonyl fluoro peptides.
A study of the reactivity of S(VI)-F containing warheads with nucleophilic amino-acid side chains under physiological conditions
Mukherjee,Debreczeni,Breed,Tentarelli,Aquila,Dowling,Whitty,Grimster
supporting information, p. 9685 - 9695 (2017/11/30)
Sulfonyl fluorides (SFs) have recently emerged as a promising warhead for the targeted covalent modification of proteins. Despite numerous examples of the successful deployment of SFs as covalent probe compounds, a detailed exploration of the factors influencing the stability and reactivity of SFs has not yet appeared. In this work we present an extensive study on the influence of steric and electronic factors on the reactivity and stability of the SF and related SVI-F groups. While SFs react rapidly with N-acetylcysteine, the resulting adducts were found to be unstable, rendering SFs inappropriate for the durable covalent inhibition of cysteine residues. In contrast, SFs afforded stable adducts with both N-acetyltyrosine and N-acetyllysine; furthermore, we show that the reactivity of arylsulfonyl fluorides towards these nucleophilic amino acids can be predictably modulated by adjusting the electronic properties of the warhead. These trends were largely conserved when the covalent reaction occurred within a protein binding pocket. We have also obtained a crystal structure depicting covalent modification of the catalytic lysine of a tyrosine kinase (FGFR1) by the ATP analog 5′-O-3-((fluorosulfonyl)benzoyl)adenosine (m-FSBA). Highly reactive warheads were demonstrated to be unstable with respect to hydrolysis in buffered aqueous solutions, indicating that warhead reactivity must be carefully tuned to provide optimal rates of protein modification. Our results demonstrate that the reactivity of SFs complements that of more commonly studied acrylamides, and we hope that this work spurs the rational design of novel SF-containing covalent probe compounds and inhibitors, particularly in cases where a suitably positioned cysteine residue is not present.
Design, synthesis, and evaluation of cell permeable probes for protein kinases
Hsu, Yu-Ling,Yang, Chun-Chieh,Chou, Tzyy-Chao,Tai, Chih-Hsuan,Chen, Long-Yuan,Fu, Shu-Ling,Lin, Jing-Jer,Lo, Lee-Chiang
, p. 58 - 68 (2015/12/23)
We have explored a novel molecular framework with a lysine core to prepare a probe library for protein kinases. Active site-directed probes, identified through screening of the library, displayed desirable labelling properties, including target specificity, good linear response to the corresponding enzymatic activity and cell permeability. Finally, a two-stage protocol utilizing the newly developed probe with an immunoprecipitation step was successfully established to monitor intracellular Src kinase activity in RK3E-v-Src cells.
