On October 28, 2020, Tokunaga, Keisuke; Sato, Mami; Kuwata, Keiko; Miura, Chizuru; Fuchida, Hirokazu; Matsunaga, Naoya; Koyanagi, Satoru; Ohdo, Shigehiro; Shindo, Naoya; Ojida, Akio published an article.Recommanded Product: Methyl N-Methylanthranilate The title of the article was Bicyclobutane Carboxylic Amide as a Cysteine-Directed Strained Electrophile for Selective Targeting of Proteins. And the article contained the following:
Expanding the repertoire of electrophiles with unique reactivity features would facilitate the development of covalent inhibitors with desirable reactivity profiles. We herein introduce bicyclo[1.1.0]butane (BCB) carboxylic amide as a new class of thiol-reactive electrophiles for selective and irreversible inhibition of targeted proteins. We first streamlined the synthetic routes to generate a variety of BCB amides. The strain-driven nucleophilic addition to BCB amides proceeded chemoselectively with cysteine thiols under neutral aqueous conditions, the rate of which was significantly slower than that of acrylamide. This reactivity profile of BCB amide was successfully exploited to develop covalent ligands targeting Bruton’s tyrosine kinase (BTK). By tuning BCB amide reactivity and optimizing its disposition on the ligand, we obtained a selective covalent inhibitor of BTK. The in-gel activity-based protein profiling and mass spectrometry-based chem. proteomics revealed that the selected BCB amide had a higher target selectivity for BTK in human cells than did a Michael acceptor probe. Further chem. proteomic study revealed that BTK probes bearing different classes of electrophiles exhibited distinct off-target profiles. This result suggests that incorporation of BCB amide as a cysteine-directed electrophile could expand the capability to develop covalent inhibitors with the desired proteome reactivity profile. The experimental process involved the reaction of Methyl N-Methylanthranilate(cas: 85-91-6).Recommanded Product: Methyl N-Methylanthranilate
The Article related to bicyclobutane carboxylic amide cysteine electrophile, Pharmacology: Effects Of Neoplasm Inhibitors and Cytotoxic Agents and other aspects.Recommanded Product: Methyl N-Methylanthranilate
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