@article{05e089247bf749349e1fd278e2a87ea4,
title = "Designed cell-penetrating peptide inhibitors of amyloid-beta aggregation and cytotoxicity",
abstract = "Henning-Knechtel et al. report that designed cell-penetrating peptides (CPPs) comprising a hydrophobic signal sequence and an amyloid-derived polycationic sequence effectively inhibit Aβ amyloidogenesis. The amyloid-derived polycationic sequences target highly conserved molecular features of amyloids, suggesting that the designed CPPs could function as general amyloid inhibitors.",
keywords = "Alzheimer's disease, aggregation, amyloid-beta peptide, cell-penetrating peptides, drug design, neurodegeneration, oligomers, prion protein, protein engineering, signal sequence",
author = "Serdal Kirmizialtin and Anja Henning-Knechtel and Gennaro Esposito and Sunil Kumar and Andrew Hamilton",
note = "Funding Information: The authors thank Dr. Renu Pasricha for providing TEM training and support. The authors also thank Ms. Maria C. Vogel for preparing the graphical abstract. NMR, TEM, and confocal fluorescence imaging experiments were carried out using the Core Technology Platforms (CTP) resources at NYU Abu Dhabi. G. Esposito thanks Mr. E. Micoli for help with NOE data collection. Additional NMR experiments were done using instrumentation in the Department of Chemistry at NYU and the Department of Biochemistry and Biophysics at Stockholm University. Computational modeling was carried out on the NYU Abu Dhabi High Performance Computing (HPC) cluster. This work was supported by funding from NYU Abu Dhabi and an Al Jalila Foundation Research Center seed grant (AJF201624) to M.M. Additional support was provided by funding from NYU to A.D.H. Stockholm University to A.G. and NYU Abu Dhabi to S.K. M.M. conceived the project. M.M. A.D.H. A.G. and S. Kirmizialtin provided funding and supervised the project. M.M. and A.H.-K. designed the amyloid formation, cell viability, and confocal imaging experiments, and A.H.-K. performed these experiments. S. Kumar performed the oligomerization experiments. C.W. performed the CD experiments. G.E. S. Kumar, A.G. J.J. and S.W. designed the NMR experiments, and G.E. S. Kumar, C.W. and S. Kr{\'o}l performed these experiments. S. Kirmizialtin and A.H.-K. designed and performed the MD simulations. M.M. and A.H.-K. wrote the manuscript with contributions from all authors. All authors reviewed and edited the final version of the manuscript. The authors declare no competing interests. Funding Information: The authors thank Dr. Renu Pasricha for providing TEM training and support. The authors also thank Ms. Maria C. Vogel for preparing the graphical abstract. NMR, TEM, and confocal fluorescence imaging experiments were carried out using the Core Technology Platforms (CTP) resources at NYU Abu Dhabi. G. Esposito thanks Mr. E. Micoli for help with NOE data collection. Additional NMR experiments were done using instrumentation in the Department of Chemistry at NYU and the Department of Biochemistry and Biophysics at Stockholm University. Computational modeling was carried out on the NYU Abu Dhabi High Performance Computing (HPC) cluster. This work was supported by funding from NYU Abu Dhabi and an Al Jalila Foundation Research Center seed grant ( AJF201624 ) to M.M. Additional support was provided by funding from NYU to A.D.H., Stockholm University to A.G., and NYU Abu Dhabi to S.K. Publisher Copyright: {\textcopyright} 2020 The Author(s)",
year = "2020",
month = feb,
day = "26",
doi = "10.1016/j.xcrp.2020.100014",
language = "English (US)",
volume = "1",
journal = "Cell Reports Physical Science",
number = "2",
}