title: Improving short antimicrobial peptides despite elusive rules for activity.
abstract: Antimicrobial peptides (AMPs) can effectively kill a broad range of life threatening multidrug-resistant bacteria, a serious threat to public health worldwide. However, despite great hopes novel drugs based on AMPs are still rare. To accelerate drug development we studied different approaches to improve the antibacterial activity of short antimicrobial peptides. Short antimicrobial peptides seem to be ideal drug candidates since they can be synthesized quickly and easily, modified and optimized. In addition, manufacturing a short peptide drug will be more cost efficient than long and structured ones. In contrast to longer and structured peptides short AMPs seem hard to design and predict. Here, we designed, synthesized and screened five different peptide libraries, each consisting of 600 9-mer peptides, against Pseudomonas aeruginosa. Each library is presenting a different approach to investigate effectiveness of an optimization strategy. The data for the 3000 peptides were analyzed using models based on fuzzy logic bioinformatics and plausible descriptors. The rate of active or superior active peptides was improved from 31.0% in a semi-random library from a previous study to 97.8% in the best new designed library. This article is part of a Special Issue entitled: Antimicrobial peptides edited by Karl Lohner and Kai Hilpert.
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute for Applied Computer Science, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Ralf
authors.initials: R
authors.lastname: Mikut
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces and Institute of Biological Interfaces 2, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Serge
authors.initials: S
authors.lastname: Ruden
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute for Applied Computer Science, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Reischl
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Microstructure Technology, P.O. Box 3640, 76021 Karlsruhe, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Breitling
authors.affiliation: Institute of Medical Immunology, Universitätsklinikum Charité, Humboldt-Universität zu Berlin, Schumannstr. 20-21, 10117 Berlin, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer
authors.affiliation: Karlsruhe Institute of Technology (KIT), Institute of Functional Interfaces and Institute of Biological Interfaces 2, P.O. Box 3640, 76021 Karlsruhe, Germany; Karlsruhe Institute of Technology (KIT), Institute of Microstructure Technology, P.O. Box 3640, 76021 Karlsruhe, Germany; Institute of Infection and Immunity, St. George's University of London, Cranmer Terrace, London, SW17 0RE, United Kingdom. Electronic address: khilpert@sgul.ac.uk.
authors.forename: Kai
authors.initials: K
authors.lastname: Hilpert
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology*; D002462:Cell Membrane / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D019295:Computational Biology; D015195:Drug Design; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D017143:Fuzzy Logic; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D019151:Peptide Library; D011550:Pseudomonas aeruginosa / Q000737:chemistry / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D019151:Peptide Library
keywords: Antimicrobial peptides; New antimicrobials; Peptide libraries; Prediction of antimicrobials; Pseudomonas aeruginosa; Short peptides