Jeffery W. Kelly
Scripps Research Institute
447 Papers
4.7K Citations
Jeffery W. Kelly is an academic researcher from Scripps Research Institute. The author has contributed to research in topics: Transthyretin & Chemistry. The author has an hindex of 108, co-authored 428 publications. Previous affiliations of Jeffery W. Kelly include University of North Carolina at Chapel Hill & Texas A&M University.
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Papers
Discovering transthyretin amyloid fibril inhibitors by limited screening
TL;DR: Several structural classes of small molecules are identified that are capable of inhibiting the TTR conformational changes facilitating amyloid fibril formation and are desirable as a promising approach to treat amyloids diseases.
164
Aromatic Sulfonyl Fluorides Covalently Kinetically Stabilize Transthyretin to Prevent Amyloidogenesis while Affording a Fluorescent Conjugate.
Neil P. Grimster,Stephen Connelly,Aleksandra Baranczak,Jiajia Dong,Larissa B. Krasnova,K. Barry Sharpless,Evan T. Powers,Ian A. Wilson,Jeffery W. Kelly +8 more
TL;DR: A library of 1,3,4-oxadiazoles substituted with a substituted aryl known to have high affinity for the inner thyroxine binding subsite of transthyretin was conceived of by structure-based design principles and synthesized.
Protein Native-State Stabilization by Placing Aromatic Side Chains in N-Glycosylated Reverse Turns
Elizabeth K. Culyba,Joshua L. Price,Sarah R. Hanson,Apratim Dhar,Chi-Huey Wong,Martin Gruebele,Evan T. Powers,Jeffery W. Kelly +7 more
TL;DR: It is shown that placing a phenylalanine residue two or three positions before a glycosylated asparagine in distinct reverse turns facilitates stabilizing interactions between the aromatic side chain and the first N-acetylglucosamine of the glycan.
AG10 inhibits amyloidogenesis and cellular toxicity of the familial amyloid cardiomyopathy-associated V122I transthyretin
Sravan C. Penchala,Stephen Connelly,Yu Wang,Miki S. Park,Lei Zhao,Aleksandra Baranczak,Irit Rappley,Hannes Vogel,Michaela Liedtke,Ronald M. Witteles,Evan T. Powers,Natàlia Reixach,William K. Chan,Ian A. Wilson,Jeffery W. Kelly,Isabella A. Graef,Mamoun M. Alhamadsheh +16 more
TL;DR: The development of AG10 is reported, a potent and selective kinetic stabilizer of TTR, which prevents dissociation of V122I-TTR in serum samples obtained from patients with familial amyloid cardiomyopathy and makes it a very promising candidate to treat TTR amyloids cardiopathy.
157
Diflunisal stabilizes familial amyloid polyneuropathy-associated transthyretin variant tetramers in serum against dissociation required for amyloidogenesis
TL;DR: It is demonstrated that the TTR heterotetramer structures in FAP patients serum are significantly less stable than that in normal subjects, indicating the instability of the variant TTR structure is a fundamental cause of TTR amyloidosis.
157