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Chemical protein synthesis to study structure and function of amyloid fibers

Abstract : Amyloid fibrils are associated with many human disorders including Alzheimer’s or Parkinson’s diseases. The formation of insoluble plaques is the result of protein misfolding and aggregation due to abnormal conformational isomerization of the involved protein. The structural and biological studies of amyloids are highly complex. In this thesis, we report on the development of different synthetic methodologies for the preparation of distinct amyloid fibril polymorphs as homogeneous samples for structural and biological studies. We also synthesized covalently-tethered oligomers composed of nine copies of an amyloidogenic peptide segment, where we were able to control the self-assembly of the structure by insertion of N-methylated amino-acids and to obtain monomeric oligomers mimicking a cross section of an amyloid fibril. We also report on the chiral recognition of L-peptides and L-proteins towards corresponding D-enantiomers during amyloid formation. Moreover, we studied various N-methylated peptide analogues to suppress amyloid growth. Overall, the results obtained in this thesis pave the way towards rational design of peptide-based inhibitors and diagnostics against amyloid propagation.
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Submitted on : Wednesday, November 21, 2018 - 3:03:06 PM
Last modification on : Thursday, November 22, 2018 - 1:19:50 AM
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  • HAL Id : tel-01929978, version 1



Régis Boehringer. Chemical protein synthesis to study structure and function of amyloid fibers. Other. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAF001⟩. ⟨tel-01929978⟩



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