title: Multidimensional Design of Anticancer Peptides.
abstract: The computer-assisted design and optimization of peptides with selective cancer cell killing activity was achieved through merging the features of anticancer peptides, cell-penetrating peptides, and tumor-homing peptides. Machine-learning classifiers identified candidate peptides that possess the predicted properties. Starting from a template amino acid sequence, peptide cytotoxicity against a range of cancer cell lines was systematically optimized while minimizing the effects on primary human endothelial cells. The computer-generated sequences featured improved cancer-cell penetration, induced cancer-cell apoptosis, and were enabled a decrease in the cytotoxic concentration of co-administered chemotherapeutic agents in vitro. This study demonstrates the potential of multidimensional machine-learning methods for rapidly obtaining peptides with the desired cellular activities.
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Yen-Chu
authors.initials: YC
authors.lastname: Lin
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Yi Fan
authors.initials: YF
authors.lastname: Lim
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Erica
authors.initials: E
authors.lastname: Russo
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Petra
authors.initials: P
authors.lastname: Schneider
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Lea
authors.initials: L
authors.lastname: Bolliger
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Adriana
authors.initials: A
authors.lastname: Edenharter
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Karl-Heinz
authors.initials: KH
authors.lastname: Altmann
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland).
authors.forename: Jan A
authors.initials: JA
authors.lastname: Hiss
authors.affiliation: Department of Chemistry and Applied Biosciences, Swiss Federal Institute of Technology (ETH), Vladimir-Prelog-Weg 4, 8093 Zurich (Switzerland). gisbert.schneider@pharma.ethz.ch.
authors.forename: Gisbert
authors.initials: G
authors.lastname: Schneider
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D057846:Cell-Penetrating Peptides / Q000494:pharmacology*; D002478:Cells, Cultured; D017076:Computer-Aided Design; D020405:Dermis / Q000166:cytology / Q000187:drug effects*; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans
chemical_list: D000970:Antineoplastic Agents; D057846:Cell-Penetrating Peptides; C000607750:decoralin
keywords: cancer; drug discovery; lipid membranes; machine learning; molecular design