Bifunctional crosslinking ligands for transthyretin

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Bifunctional crosslinking ligands for transthyretin

Wild-type and variant forms of transthyretin (TTR), a normal plasma protein, are amyloidogenic and can be deposited in the tissues as amyloid fibrils causing acquired and hereditary systemic TTR amyloidosis, a debilitating and usually fatal disease. Reduction in the abundance of amyloid fibril precursor proteins arrests amyloid deposition and halts disease progression in all forms of amyloidosi...

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Bifunctional coumarin derivatives that inhibit transthyretin amyloidogenesis and serve as fluorescent transthyretin folding sensors.

We describe coumarin derivatives that are non-fluorescent in aqueous buffers and that very selectively bind to transthyretin (TTR) in complex biological environments potently inhibiting TTR amyloidogenesis while also exhibiting sensitive off-on fluorescent sensing of the properly folded quaternary structure of TTR.

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Trapping of palindromic ligands within native transthyretin prevents amyloid formation.

Transthyretin (TTR) amyloidosis is a fatal disease for which new therapeutic approaches are urgently needed. We have designed two palindromic ligands, 2,2'-(4,4'-(heptane-1,7-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (mds84) and 2,2'-(4,4'-(undecane-1,11-diylbis(oxy))bis(3,5-dichloro-4,1-phenylene)) bis(azanediyl)dibenzoic acid (4ajm15), that are rapidly bound b...

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Disuccinimidyl esters as bifunctional crosslinking reagents for proteins: assays with myosin.

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Cell Adhesion to Unnatural Ligands Mediated by a Bifunctional Protein

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ژورنال

عنوان ژورنال: Open Biology

سال: 2015

ISSN: 2046-2441

DOI: 10.1098/rsob.150105