Chen, Yen-Shan; Gleaton, Jeremy; Yang, Yanwu; Dhayalan, Balamurugan; Phillips, Nelson B.; Liu, Yule; Broadwater, Laurie; Jarosinski, Mark A.; Chatterjee, Deepak; Lawrence, Michael C.; Hattier, Thomas; Michael, M. Dodson; Weiss, Michael A. published an article in 2021. The article was titled 《Insertion of a synthetic switch into insulin provides metabolite-dependent regulation of hormone-receptor activation》, and you may find the article in Proceedings of the National Academy of Sciences of the United States of America.COA of Formula: C6H6BFO2 The information in the text is summarized as follows:
Insulin-signaling requires conformational change: whereas the free hormone and its receptor each adopt autoinhibited conformations, their binding leads to structural reorganization. To test the functional coupling between insulins hinge opening and receptor activation, we inserted an artificial ligand-dependent switch into the insulin mol. Ligand-binding disrupts an internal tether designed to stabilize the hormone native closed and inactive conformation, thereby enabling productive receptor engagement. This scheme exploited a diol sensor (meta-fluoro-phenylboronic acid at GlyA1) and internal diol (3,4-dihydroxybenzoate at LysB28). The sensor recognizes monosaccharides (fructose > glucose). Studies of insulin-signaling in human hepatoma-derived cells (HepG2) demonstrated fructose-dependent receptor autophosphorylation leading to appropriate downstream signaling events, including a specific kinase cascade and metabolic gene regulation (gluconeogenesis and lipogenesis). Addition of glucose (an isomeric ligand with negligible sensor affinity) did not activate the hormone. Similarly, metabolite-regulated signaling was not observed in control studies of 1) an unmodified insulin analog or 2) an analog containing a diol sensor without internal tethering. Although secondary structure (as probed by CD) was unaffected by ligand-binding, heteronuclear NMR studies revealed subtle local and nonlocal monosaccharide-dependent changes in structure. Insertion of a synthetic switch into insulin has thus demonstrated coupling between hinge-opening and allosteric holoreceptor signaling. In addition to this foundational finding, our results provide proof of principle for design of a mechanism-based metabolite-responsive insulin. In particular, replacement of the present fructose sensor by an analogous glucose sensor may enable translational development of a smart insulin analog to mitigate hypoglycemic risk in diabetes therapy. After reading the article, we found that the author used (3-Fluorophenyl)boronic acid(cas: 768-35-4COA of Formula: C6H6BFO2)
(3-Fluorophenyl)boronic acid(cas: 768-35-4) can be used to make novel liquid crystalline fluorobiphenylcyclohexenes and difluoroterphenyls by palladium-catalyzed cross-couplings also used in the synthesis of o-phenylphenols as potent leukotriene B4 receptor agonists.COA of Formula: C6H6BFO2
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics