Design and activity of a cyclic mini-β-defensin analog: a novel antimicrobial tool.
We have designed a cyclic 17-amino acid β-defensin analog featuring a single disulfide bond. This analog, designated "AMC" (ie, antimicrobial cyclic peptide), combines the internal hydrophobic domain of hBD1 and the C-terminal charged region of hBD3. The novel peptide was synthesized and characterized by nuclear magnetic resonance spectroscopy. The antimicrobial activities against gram-positive and gram-negative bacteria as well as against herpes simplex virus type 1 were analyzed. The cytotoxicity and serum stability were assessed. Nuclear magnetic resonance of AMC in aqueous solution suggests that the structure of the hBD1 region, although not identical, is preserved. Like the parent defensins, AMC is not cytotoxic for CaCo-2 cells. Interestingly, AMC retains the antibacterial activity of the parent hBD1 and hBD3 against Pseudomonas aeruginosa, Enterococcus faecalis, and Escherichia coli, and exerts dose-dependent activity against herpes simplex virus type 1. Moreover, while the antibacterial and antiviral activities of the oxidized and reduced forms of the parent defensins are similar, those of AMC are significantly different, and oxidized AMC is also considerably more stable in human serum. Taken together, our data also suggest that this novel peptide may be added to the arsenal of tools available to combat antibiotic-resistant infectious diseases, particularly because of its potential for encapsulation in a nanomedicine vector.
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy ; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy.
Olga
O
Scudiero
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy.
Ersilia
E
Nigro
Dipartimento di Farmacia, Università di Napoli Federico II, Naples, Italy.
Marco
M
Cantisani
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy.
Irene
I
Colavita
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
Marilisa
M
Leone
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
Flavia Anna
FA
Mercurio
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli, Naples, Italy.
Massimiliano
M
Galdiero
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy.
Antonello
A
Pessi
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy ; Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università di Napoli, Caserta, Italy.
Aurora
A
Daniele
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy ; Dipartimento di Medicina Molecolare e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy ; IRCCS Fondazione SDN, Naples, Italy.
Francesco
F
Salvatore
Dipartimento di Farmacia, Università di Napoli Federico II, Naples, Italy ; Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy.
Stefania
S
Galdiero
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D018938:Caco-2 Cells; D004220:Disulfides / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004355:Drug Stability; D018259:Herpesvirus 1, Human / Q000187:drug effects; D006801:Humans; D008969:Molecular Sequence Data; D023083:beta-Defensins / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000998:Antiviral Agents; D004220:Disulfides; D023083:beta-Defensins
antimicrobial activity; cyclic mini-peptide; human beta-defensin