title: Rational design of artificial β-strand-forming antimicrobial peptides with biocompatible properties.
abstract: Because the intensive use of antibiotics has led to a large variety of resistant bacterial strains, therapeutic measures have become increasingly challenging. In order to ensure reliable treatment of diseases, alternative antimicrobial agents need to be explored. In this context, antimicrobial peptides have been discussed as novel bioactive molecules, which, however, may be limited in their applicability due to their high manufacturing costs and poor pharmacokinetic properties. Consequently, the design of artificial antimicrobial peptides featuring two flanking cationic regions and a hydrophobic center is presented. These sequences led to distinct antimicrobial activity on the same order of magnitude as that of naturally occurring reference peptides but with less cytotoxic or cytostatic drawbacks. Furthermore, a deletion and substitution library revealed the minimal sequence requirements. By analysis of the computed 3D structures of these peptides, a single characteristic β-strand was identified. This structural motif was pivotal for antimicrobial activity. Consequently, an optimized peptide sequence with antimicrobial and biocompatible properties was derived, and its application was demonstrated in a mixed culture experiment. Thus, it was shown that the optimized artificial antimicrobial peptide is suitable as a therapeutic agent and may be used as template for the development of new antimicrobial peptides with unique secondary structures.
authors.affiliation: Fraunhofer Institute for Biomedical Engineering IBMT , Branch Potsdam, Am Muehlenberg 13, 14476 Potsdam, Germany.
authors.forename: Karsten
authors.initials: K
authors.lastname: Rapsch
authors.forename: Frank F
authors.initials: FF
authors.lastname: Bier
authors.forename: Markus
authors.initials: M
authors.lastname: von Nickisch-Rosenegk
mesh_terms: D000890:Anti-Infective Agents / Q000737:chemistry*; D001672:Biocompatible Materials / Q000737:chemistry*; D008962:Models, Theoretical; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000890:Anti-Infective Agents; D001672:Biocompatible Materials; D010455:Peptides
keywords: antimicrobial peptide; mode of action; permeability; secondary structure; therapy