| Title: | Effective Design of Multifunctional Peptides by Combining Compatible Functions |
| Author(s): | Diener C; Garza Ramos Martinez G; Moreno Blas D; Castillo Gonzalez DA; Corzo G; Castro-Obregon S; Del Rio G; |
| Address: | "Department of Biochemistry and Structural Biology, Institute of Cellular Physiology, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. Department of Biochemistry, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. Department of Neurodevelopment and Physiology, Institute of Cellular Physiology, Universidad Nacional Autonoma de Mexico, Mexico City, Mexico. Department of Molecular Medicine and Bioprocesses, Institute of Biotechnology, Universidad Nacional Autonoma de Mexico, Cuernavaca Morelos, Mexico" |
| DOI: | 10.1371/journal.pcbi.1004786 |
| ISSN/ISBN: | 1553-7358 (Electronic) 1553-734X (Print) 1553-734X (Linking) |
| Abstract: | "Multifunctionality is a common trait of many natural proteins and peptides, yet the rules to generate such multifunctionality remain unclear. We propose that the rules defining some protein/peptide functions are compatible. To explore this hypothesis, we trained a computational method to predict cell-penetrating peptides at the sequence level and learned that antimicrobial peptides and DNA-binding proteins are compatible with the rules of our predictor. Based on this finding, we expected that designing peptides for CPP activity may render AMP and DNA-binding activities. To test this prediction, we designed peptides that embedded two independent functional domains (nuclear localization and yeast pheromone activity), linked by optimizing their composition to fit the rules characterizing cell-penetrating peptides. These peptides presented effective cell penetration, DNA-binding, pheromone and antimicrobial activities, thus confirming the effectiveness of our computational approach to design multifunctional peptides with potential therapeutic uses. Our computational implementation is available at http://bis.ifc.unam.mx/en/software/dcf" |
| Keywords: | "Algorithms Amino Acid Sequence Animals Antimicrobial Cationic Peptides/chemistry/genetics/physiology Cell-Penetrating Peptides/chemistry/genetics/physiology Cells, Cultured Computational Biology DNA-Binding Proteins/chemistry/genetics/physiology *Drug Des;" |
| Notes: | "MedlineDiener, Christian Garza Ramos Martinez, Georgina Moreno Blas, Daniel Castillo Gonzalez, David A Corzo, Gerardo Castro-Obregon, Susana Del Rio, Gabriel eng Research Support, Non-U.S. Gov't 2016/04/21 PLoS Comput Biol. 2016 Apr 20; 12(4):e1004786. doi: 10.1371/journal.pcbi.1004786. eCollection 2016 Apr" |
