Total chemical synthesis and biophysical properties of a designed soluble 24 kDa amyloid analogue. Issue 25 (7th June 2018)

• Record Type: Journal Article
• Authors: Boehringer, Régis; Kieffer, Bruno; Torbeev, Vladimir
• Is Part Of: Chemical science. Volume 9:Issue 25(2018)
• Page Start: 5594
• Page End: 5599
• Publication Date: 2018-06-07
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/c8sc01790e
• Languages: English
• ISSNs: 2041-6520

Abstract

Abstract : A soluble amyloid analogue was designed and prepared by total chemical synthesis using native chemical ligation. Abstract : Discovering molecular probes that specifically recognize distinct amyloid structures is highly important for physiological studies of protein-misfolding diseases as well as for the development of diagnostic reagents and inhibitors of amyloid self-assembly. Here, we demonstrate an approach that allows for identification of N -methylated peptides that are specific binders for a particular amyloid fiber subtype (or polymorph). Protein design and chemical synthesis were used to produce covalently tethered amyloid analogues with molecular masses approaching 24 kDa and containing nine copies of an amyloidogenic peptide. Such engineered constructs served as a molecular testing platform to evaluate the aggregation properties and solubility as a function of N -methylation pattern. An advantage of the method is the possibility of biophysical characterization of amyloid constructs in solution.