Aromatic sulfonyl fluorides covalently kinetically stabilize transthyretin to prevent amyloidogenesis while affording a fluorescent conjugate

NP Grimster, S Connelly, A Baranczak…

Index: Grimster, Neil P.; Connelly, Stephen; Baranczak, Aleksandra; Dong, Jiajia; Krasnova, Larissa B.; Sharpless, K. Barry; Powers, Evan T.; Wilson, Ian A.; Kelly, Jeffery W. Journal of the American Chemical Society, 2013 , vol. 135, # 15 p. 5656 - 5668

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Citation Number: 28

Abstract

Molecules that bind selectively to a given protein and then undergo a rapid chemoselective reaction to form a covalent conjugate have utility in drug development. Herein a library of 1, 3, 4-oxadiazoles substituted at the 2 position with an aryl sulfonyl fluoride and at the 5 position with a substituted aryl known to have high affinity for the inner thyroxine binding subsite of transthyretin (TTR) was conceived of by structure-based design principles and ...