324769-06-4Relevant articles and documents
Protein Modification at Tyrosine with Iminoxyl Radicals
Ishiyama, Takashi,Kanai, Motomu,Maruyama, Katsuya,Oisaki, Kounosuke,Sakai, Kentaro,Seki, Yohei,Togo, Takaya
supporting information, p. 19844 - 19855 (2021/11/30)
Post-translational modifications (PTMs) of proteins are a biological mechanism for reversibly controlling protein function. Synthetic protein modifications (SPMs) at specific canonical amino acids can mimic PTMs. However, reversible SPMs at hydrophobic amino acid residues in proteins are especially limited. Here, we report a tyrosine (Tyr)-selective SPM utilizing persistent iminoxyl radicals, which are readily generated from sterically hindered oximes via single-electron oxidation. The reactivity of iminoxyl radicals with Tyr was dependent on the steric and electronic demands of oximes; isopropyl methyl piperidinium oxime 1f formed stable adducts, whereas the reaction of tert-butyl methyl piperidinium oxime 1o was reversible. The difference in reversibility between 1f and 1o, differentiated only by one methyl group, is due to the stability of iminoxyl radicals, which is partly dictated by the bond dissociation energy of oxime O-H groups. The Tyr-selective modifications with 1f and 1o proceeded under physiologically relevant, mild conditions. Specifically, the stable Tyr-modification with 1f introduced functional small molecules, including an azobenzene photoswitch, to proteins. Moreover, masking critical Tyr residues by SPM with 1o, and subsequent deconjugation triggered by the treatment with a thiol, enabled on-demand control of protein functions. We applied this reversible Tyr modification with 1o to alter an enzymatic activity and the binding affinity of a monoclonal antibody with an antigen upon modification/deconjugation. The on-demand ON/OFF switch of protein functions through Tyr-selective and reversible covalent-bond formation will provide unique opportunities in biological research and therapeutics.
5- or 6-substituted benzofuran-2-carboxamide compounds and methods for using them
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, (2016/09/12)
The disclosure relates particularly to certain carboxamide, sulfonamide and amine compounds and pharmaceutical compositions thereof, and to methods of treating and ameliorating disorders and conditions related to the adiponectin pathway, sphingolipid metabolism, oxidative stress, mitochondrial dysfunction, free radical damage and metabolic inefficiency, among others. In certain embodiments, the compounds have the structures (I-1), (2-I) and (3-I) in which the variables are as described herein.
SUBSTITUTED BENZAMIDES AND METHODS OF USE THEREOF
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Page/Page column 675, (2015/06/11)
The invention provides compounds having the general formula I, and pharmaceutically acceptable salts thereof, wherein the variables RA, RAA, subscript n, ring A, X2, L, subscript m, X1, R1, R2, R3, R4, R5, and RN have the meaning as described herein, and compositions containing such compounds and methods for using such compounds and compositions.