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β‐Sheet Breaker Peptides Containing α,β‐Dehydrophenylalanine: Synthesis and In Vitro Activity Studies
Author(s) -
Giordano Cesare,
Punzi Pasqualina,
Lori Clorinda,
Chiaraluce Roberta,
Consalvi Valerio
Publication year - 2014
Publication title -
chempluschem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.801
H-Index - 61
ISSN - 2192-6506
DOI - 10.1002/cplu.201402072
Subject(s) - chemistry , fibrillogenesis , circular dichroism , electrospray ionization , thioflavin , stereochemistry , peptide , pentapeptide repeat , lipophilicity , mass spectrometry , fourier transform infrared spectroscopy , in vitro , biochemistry , chromatography , quantum mechanics , alzheimer's disease , medicine , physics , disease , pathology
The synthesis and fibrillogenesis‐inhibiting activity of the new peptide derivatives 1 – 6 , containing α,β‐unsaturated phenylalanines, are reported. These compounds are related to the pentapeptide Ac‐LPFFD‐NH 2 ( i Aβ5p ), which was designed by Soto and co‐workers and is commonly accepted as a lead compound for fibrillogenesis inhibition . Their activities are determined by Thioflavin T binding assay, far‐UV circular dichroism (CD) spectroscopy , and SEM; in addition, their structures in solution are studied through far‐UV CD and FTIR spectroscopy. The presence of two α,β‐unsaturated phenylalanines increases the fibrillogenesis inhibiting activity significantly in comparison with the lead compound. The interactions between the Aβ 1–40 and the inhibitors using electrospray ionization mass spectrometry are also studied. The analyses prove the presence of noncovalent complexes of Aβ 1–40 with i Aβ5p and its derivatives 1 – 3 with stoichiometries of 1:1 and 2:1, and the results are independent of time and Aβ 1–40 /inhibitor ratio.