Β‐Sheet Breaker Peptides Containing α, β‐Dehydrophenylalanine: Synthesis and In Vitro Activity Studies. Issue 7 (6th May 2014)

• Record Type: Journal Article
• Authors: Giordano, Cesare; Punzi, Pasqualina; Lori, Clorinda; Chiaraluce, Roberta; Consalvi, Valerio
• Is Part Of: ChemPlusChem. Volume 79:Issue 7(2014:Jul.)
• Page Start: 1036
• Page End: 1043
• Publication Date: 2014-05-06
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1002/cplu.201402072
• Languages: English
• ISSNs: 2192-6506

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>The synthesis and fibrillogenesis‐inhibiting activity of the new peptide derivatives <bold>1</bold>–<bold>6</bold>, containing α, β‐unsaturated phenylalanines, are reported. These compounds are related to the pentapeptide Ac‐LPFFD‐NH₂ (<italic><bold>i</bold></italic><bold>Aβ5p</bold>), 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 <italic><bold>i</bold></italic><bold>Aβ5p</bold> and its derivatives <bold>1</bold>–<bold>3</bold> with stoichiometries of 1:1 and 2:1, and the results are independent of time and Aβ_1–40/inhibitor ratio.</p> </abstract>