ArticleJournal of the American Chemical Society2013
Stilbene vinyl sulfonamides as fluorogenic sensors of and traceless covalent kinetic stabilizers of transthyretin that prevent amyloidogenesis.
Article in Journal of the American Chemical Society, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 43 citations in OpenAlex.
- Application of SITS in the Electrochemical Biosensor Method for Characterization of Substrate Transport into Microbial Cells.Current microbiology · 2026Article
- Covalent Modulation of Protein Misfolding and Aggregation Processes in the Context of Neurodegenerative Diseases.Archiv der Pharmazie · 2026Review
- Inhibitors of Transthyretin Amyloidosis: How to Rank Drug Candidates Using X-ray Crystallography Data.Molecules (Basel, Switzerland) · 2024Article
- A proteome-wide atlas of lysine-reactive chemistry.Nature chemistry · 2021Article
- Fluorotryptophan Incorporation Modulates the Structure and Stability of Transthyretin in a Site-Specific Manner.Biochemistry · 2017Article
- Stilbene Boronic Acids Form a Covalent Bond with Human Transthyretin and Inhibit Its Aggregation.Journal of medicinal chemistry · 2017Article
- Latent analysis of unmodified biomolecules and their complexes in solution with attomole detection sensitivity.Nature chemistry · 2015Article
- Spectral fine tuning of cyanine dyes: electron donor-acceptor substituted analogues of thiazole orange.Photochemical & photobiological sciences : Official journal of the European Photochemistry Association and the European Society for Photobiology · 2015Article
- Fluorescence Turn-On Folding Sensor To Monitor Proteome Stress in Live Cells.Journal of the American Chemical Society · 2015Article
- A fluorogenic aryl fluorosulfate for intraorganellar transthyretin imaging in living cells and in Caenorhabditis elegans.Journal of the American Chemical Society · 2015Article
- De novo-designed enzymes as small-molecule-regulated fluorescence imaging tags and fluorescent reporters.Journal of the American Chemical Society · 2014Article
- Small molecule probes to quantify the functional fraction of a specific protein in a cell with minimal folding equilibrium shifts.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Small molecules that react selectively with a specific non-enzyme drug-target protein in a complex biological environment without displacement of a leaving group (tracelessly) are rare and highly desirable. Herein we describe the development of a family of fluorogenic stilbene-based vinyl amides and vinyl sulfonamides that covalently modify transthyretin (TTR) tracelessly. These small molecules bind selectively to TTR in complex biological environments and then undergo a rapid and chemoselective 1,4-Michael addition with the pKa-perturbed Lys-15 ε-amino group of TTR. Replacing the vinyl amide in 2 with the more reactive vinyl sulfonamide in 4 hastens the conjugation kinetics. X-ray cocrystallography verified the formation of the secondary amine bond mediating the conjugation in the case of 2 and 4 and confirmed the expected orientation of the stilbene within the TTR binding sites. Vinyl amide 2 and vinyl sulfonamide 4 potently inhibit TTR dissociation and amyloid fibril formation in vitro. The TTR binding selectivity, modification yield, and reaction chemoselectivity of vinyl sulfonamide 4 are good enough in human plasma to serve as a starting point for medicinal chemistry efforts. Moreover, vinyl sulfonamide 4 is fluorogenic: it exhibits minimal background fluorescence in complex biological environments, remains dark upon binding to TTR, and becomes fluorescent only upon reaction with TTR. The fluorogenicity of 4 was utilized to accurately quantify the native TTR concentration in Escherichia coli lysate using a fluorescence plate reader.
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