Abstract
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 language | English |
|---|---|
| Pages (from-to) | 2665-2672 |
| Number of pages | 8 |
| Journal | Antimicrobial Agents and Chemotherapy |
| Volume | 49 |
| Issue number | 7 |
| DOIs | |
| Publication status | Published - Jul 2005 |
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ASJC Scopus subject areas
- Pharmacology (medical)
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Antimicrobial activity of novel dendrimeric peptides obtained by phage display selection and rational modification. / Pini, Alessandro; Giuliani, Andrea; Falciani, Chiara; Runci, Ylenia; Ricci, Claudia; Lelli, Barbara; Malossi, Monica; Neri, Paolo; Rossolini, Gian Maria; Bracci, Luisa.
In: Antimicrobial Agents and Chemotherapy, Vol. 49, No. 7, 07.2005, p. 2665-2672.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antimicrobial activity of novel dendrimeric peptides obtained by phage display selection and rational modification
AU - Pini, Alessandro
AU - Giuliani, Andrea
AU - Falciani, Chiara
AU - Runci, Ylenia
AU - Ricci, Claudia
AU - Lelli, Barbara
AU - Malossi, Monica
AU - Neri, Paolo
AU - Rossolini, Gian Maria
AU - Bracci, Luisa
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=21444448725&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=21444448725&partnerID=8YFLogxK
U2 - 10.1128/AAC.49.7.2665-2672.2005
DO - 10.1128/AAC.49.7.2665-2672.2005
M3 - Article
C2 - 15980334
AN - SCOPUS:21444448725
VL - 49
SP - 2665
EP - 2672
JO - Antimicrobial Agents and Chemotherapy
JF - Antimicrobial Agents and Chemotherapy
SN - 0066-4804
IS - 7
ER -