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Using chiral peptide substitutions to probe the structure function relationship of a key residue of Aβ42
C.J.A. Warner, , A.R. Foley, E. Chen, D.S. Kliger, J.A. Raskatov
Published in John Wiley and Sons Inc
PMID: 27933649
Volume: 29
Issue: 1
Pages: 5 - 9
Amyloid beta-protein 42 plays an important role in the onset and progression of Alzheimer's disease. Familial mutations have identified the glutamate residue 22 as a hotspot with regard to peptide neurotoxicity. We introduce an approach to study the influence of systematic sidechain modification at this residue, employing chirality as a structural probe. Circular dichroism experiments reveal that charge-preserving alterations of the amino acid sidechain attenuate the characteristic random coil to β-sheet transition associated with the wildtype peptide. Removal of the negative charge from residue 22, a trait observed with all known familial mutations at this residue, gives rise to a peptide with limited random coil propensity and high β-sheet characteristics. Our approach can be extended to other residues of Aβ, as well as further amyloidogenic peptides. © 2016 Wiley Periodicals, Inc.
About the journal
JournalData powered by TypesetChirality
PublisherData powered by TypesetJohn Wiley and Sons Inc