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A hIAPP‐derived all‐ d ‐amino‐acid inhibits hIAPP fibrillation efficiently at membrane surface by targeting α‐helical oligomeric intermediates
Author(s) -
Wang Li,
Lei Liyan,
Li Yang,
Wang Liping,
Li Fei
Publication year - 2014
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2014.02.020
Subject(s) - biophysics , chemistry , membrane , fibrillation , amino acid , biochemistry , biology , atrial fibrillation , medicine , cardiology
A variety of peptides and peptide derivatives have been constructed using the “β‐sheet core segment” of amyloid proteins as inhibitors of amyloidogenic fibrillation. A novel all‐ d ‐amino‐acid from hIAPP β‐sheet core segment (hIAPP 22–27) is demonstrated to inhibit hIAPP fibril formation efficiently both at the phospholipid membrane and in bulk solution. The inhibitor terminates hIAPP aggregation to the α‐helical oligomeric intermediates at the membrane surface, whereas it stops the aggregation at the stage of β‐sheet oligomeric intermediates in bulk solution. This is the first evidence that the inhibition mechanism of the inhibitor at membrane surface is significantly different from that in bulk solution.