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Antimicrobial Agents and Chemotherapy, July 2005, p. 2665-2672, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2665-2672.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Antimicrobial Activity of Novel Dendrimeric Peptides Obtained by Phage Display Selection and Rational Modification

Alessandro Pini,1*,{dagger} Andrea Giuliani,1,{dagger} Chiara Falciani,1 Ylenia Runci,1 Claudia Ricci,1 Barbara Lelli,1 Monica Malossi,2 Paolo Neri,1 Gian Maria Rossolini,2 and Luisa Bracci1

Sezione di Biochimica,1 Sezione di Microbiologia, Dipartimento di Biologia Molecolare, Università degli Studi di Siena, 53100 Siena, Italy2

Received 25 November 2004/ Returned for modification 16 January 2005/ Accepted 23 March 2005

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.

* Corresponding author. Mailing address: Dipartimento di Biologia Molecolare, Università degli Studi di Siena, Via Fiorentina 1, 53100 Siena, Italy. Phone: 39 0577 234921. Fax: 39 0577 234903. E-mail: pinia{at}unisi.it.

{dagger} These two authors contributed equally to the work.

Antimicrobial Agents and Chemotherapy, July 2005, p. 2665-2672, Vol. 49, No. 7
0066-4804/05/$08.00+0     doi:10.1128/AAC.49.7.2665-2672.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Tanaka, T., Kokuryu, Y., Matsunaga, T. (2008). Novel Method for Selection of Antimicrobial Peptides from a Phage Display Library by Use of Bacterial Magnetic Particles. Appl. Environ. Microbiol. 74: 7600-7606 [Abstract] [Full Text]  


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