| Autor: |
Shi C; Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France., Kaffy J; Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France., Ha-Duong T; Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France., Gallard JF; Equipe Biologie et Chimie Structurales, Dept Chimie et Biologie Structurales et Analytiques, ICSN CNRS, Université Paris Saclay, 1 avenue de la terrasse, 91190 Gif sur Yvette, France., Pruvost A; CEA, INRAE, Département Médicaments et Technologies pour La Santé, Université Paris-Saclay, SPI 91191 Gif-sur-Yvette, France., Mabondzo A; CEA, INRAE, Département Médicaments et Technologies pour La Santé, Université Paris-Saclay, SPI 91191 Gif-sur-Yvette, France., Ciccone L; Department of Pharmacy, University of Pisa, 56126 Pisa, Italy., Ongeri S; Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France., Tonali N; Université Paris-Saclay, CNRS, BioCIS, Bat. Henri Moissan, 17 av. des Sciences, 91400 Orsay, France. |
| Abstrakt: |
A novel class of peptidomimetic foldamers based on diaza-peptide units are reported. Circular dichroism, attenuated total reflection -Fourier transform infrared, NMR, and molecular dynamics studies demonstrate that unlike the natural parent nonapeptide, the specific incorporation of one diaza-peptide unit at the N-terminus allows helical folding in water, which is further reinforced by the introduction of a second unit at the C-terminus. The ability of these foldamers to resist proteolysis, to mimic the small helical hot spot of transthyretin-amyloid β (Aβ) cross-interaction, and to decrease pathological Aβ aggregation demonstrates that the introduction of diaza-peptide units is a valid approach for designing mimics or inhibitors of protein-protein interaction and other therapeutic peptidomimetics. This study also reveals that small peptide foldamers can play the same role as physiological chaperone proteins and opens a new way to design inhibitors of amyloid protein aggregation, a hallmark of more than 20 serious human diseases such as Alzheimer's disease. |
