Antimicrobial activity of novel dendrimeric peptides obtained by phage display selection and rational modification

Alessandro Pini, Andrea Giuliani, Chiara Falciani, Ylenia Runci, Claudia Ricci, Barbara Lelli, Monica Malossi, Paolo Neri, Gian Maria Rossolini, Luisa Bracci

Research output: Contribution to journalArticlepeer-review


A large 10-mer phage peptide library was panned against whole Escherichia coli cells, and an antimicrobial peptide (QEKIRVRLSA) was selected. The peptide was synthesized in monomeric and dendrimeric tetrabranched form (multiple antigen peptide [MAP]), which generally allows a dramatic increase of peptide stability to peptidases and proteases. The antibacterial activity of the dendrimeric peptide against E. coli was much higher than that of the monomeric form. Modification of the original sequence, by residue substitution or sequence shortening, produced three different MAPs, M4 (QAKIRVRLSA), M5 (KIRVRLSA), and M6 (QKKIRVRLSA) with enhanced stability to natural degradation and antimicrobial activity against a large panel of gram-negative bacteria. The MICs of the most potent peptide, M6, were as low as 4 to 8 μg/ml against recent clinical isolates of multidrug-resistant Pseudomonas aeruginosa and members of the Enterobacteriaceae. The same dendrimeric peptides showed high stability to blood proteases, low hemolytic activity, and low cytotoxic effects on eukaryotic cells, making them promising candidates for the development of new antibacterial drugs.

Original languageEnglish
Pages (from-to)2665-2672
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Issue number7
Publication statusPublished - Jul 2005

ASJC Scopus subject areas

  • Pharmacology (medical)


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