Combining Topology and Sequence Design for the Discovery of Potent Antimicrobial Peptide Dendrimers against Multidrug-Resistant Pseudomonas aeruginosa

• Published in: Angewandte Chemie Vol. 126; no. 47; pp. 13041 - 13045
• Main Authors: Stach, Michaela, Siriwardena, Thissa N., Köhler, Thilo, van Delden, Christian, Darbre, Tamis, Reymond, Jean-Louis
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 17.11.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Antibiotika; Antiinfectives and antibacterials; Antimicrobial agents; Antimikrobielle Peptide; Bacteria; Bacteriology; Chemistry; Dendrimere; Dendrimers; Design engineering; Pathogens; Peptide; Peptides; Pseudomonas aeruginosa; Public health; Topology
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.201409270

Multidrug‐resistant opportunistic bacteria, such as Pseudomonas aeruginosa, represent a major public health threat. Antimicrobial peptides (AMPs) and related peptidomimetic systems offer an attractive opportunity to control these pathogens. AMP dendrimers (AMPDs) with high activity against multidrug‐resistant clinical isolates of P. aeruginosa and Acinetobacter baumannii were now identified by a systematic survey of the peptide sequences within the branches of a distinct type of third‐generation peptide dendrimers. Combined topology and peptide sequence design as illustrated here represents a new and general strategy to discover new antimicrobial agents to fight multidrug‐resistant bacterial pathogens. Multiresistente Bakterien wie Pseudomonas aeruginosa und Acinetobacter baumannii stellen eine Bedrohung für die öffentliche Gesundheit dar. Das kombinierte Design von Topologie und Aminosäuresequenz führte zu neuen antimikrobiellen Peptid‐Dendrimeren mit hoher Aktivität gegen diese Pathogene, was einen neuen und allgemeinen Ansatz zur Entdeckung antimikrobieller Wirkstoffe darstellt.