Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines
Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines(552 views) Scudiero O, Galdiero S, Nigro E, Del Vecchio L, Di Noto R, Cantisani M, Colavita I, Galdiero M, Cassiman JJ, Daniele A, Pedone C, Salvatore F
CEINGE-Biotecnologie Avanzate Scarl, Naples, Italy.
Dipartimento di Biochimica e Biotecnologie Mediche, Università Degli Studi di Napoli Federico II, Naples, Italy
Dipartimento di Farmacia, Università Degli Studi di Napoli Federico II, Naples, Italy
Centro Interuniversitario di Ricerca sui Peptidi Bioattivi, Naples, Italy
IRCCSFondazione SDN, Naples, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli, Naples, Italy
Center for Human Genetics, Campus St. Rafael, Leuven, Belgium
Dipartimento di Scienze e Tecnologie Ambientali Biologiche Farmaceutiche, Seconda Università Degli Studi di Napoli, Caserta, Italy
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Hoover, D. M., Wu, Z., Tucker, K., Lu, W., Lubkowski, J., Antimicrobial characterization of human beta-defensin 3 derivatives (2003) Antimicrob. Agents Chemother., 47, pp. 2804-2809
Kl ver, E., Schulz-Maronde, S., Scheid, S., Meyer, B., Forssmann, W. G., Adermann, K., Structure-activity relation of human beta-defensin 3: Influence of disulfide bonds and cysteine substitution on antimicrobial activity and cytotoxicity (2005) Biochemistry, 44, pp. 9804-9816
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Lehrer, R. I., Peptide gets in shape for self-defence (2011) Nature, 469, pp. 309-310
Conejo-Garcia, J. R., Jaumann, F., Schulz, S., Krause, A., Rodr guez- Jim nez, J., Forssmann, U., Adermann, K., Bals, R., Identification of a novel, multifunctional beta-defensin (human beta-defensin 3) with specific antimicrobial activity (2001) Cell Tissue Res, 306, pp. 257-264
Weinberg, A., Qui ones-Mateu, M. E., Lederman, M. M., Role of human beta-defensins in HIV infection (2006) Adv. Dent. Res., 19, pp. 42-48
Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines
Human beta-defensins (hBDs) are crucial peptides for the innate immune response and are thus prime candidates as therapeutic agents directed against infective diseases. Based on the properties of wild-type hBD1 and hBD3 and of previously synthesized analogs (1C, 3I, and 3N), we have designed a new analog, 3NI, and investigated its potential as an antimicrobial drug. Specifically, we evaluated the antimicrobial activities of 3NI versus those of hBD1, hBD3, 1C, 3I, and 3N. Our results show that 3NI exerted greater antibacterial activity against Pseudomonas aeruginosa, Escherichia coli, and Enterococcus faecalis than did hBD1 and hBD3, even with elevated salt concentrations. Moreover, its antiviral activity against herpes simplex virus 1 was greater than that of hBD1 and similar to that of hBD3. Subsequently, we investigated the cytotoxic effects of all peptides in three human epithelial carcinoma cell lines: A549 from lung, CaCo-2 from colon, and Capan-1 from pancreas. None of the analogs significantly reduced cell viability versus wild-type hBD1 and hBD3. They did not induce genotoxicity or cause an increase in the number of apoptotic cells. Using confocal microscopy, we also investigated the localization of the peptides during their incubation with epithelial cells and found that they were distributed on the cell surface, from which they were internalized. Finally, we show that hBD1 and hBD3 are characterized by high resistance to serum degradation. In conclusion, the new analog 3NI seems to be a promising anti-infective agent, particularly given its high salt resistance--a feature that is relevant in diseases such as cystic fibrosis.
Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines
Chimeric beta-defensin analogs, including the novel 3NI analog, display salt-resistant antimicrobial activity and lack toxicity in human epithelial cell lines
Petraglia F, Singh AA, Carafa V, Nebbioso A, Conte M, Scisciola L, Valente S, Baldi A, Mandoli A, Petrizzi VB, Ingenito C, De Falco S, Cicatiello V, Apicella I, Janssen-megens EM, Kim B, Yi G, Logie C, Heath S, Ruvo M, Wierenga ATJ, Flicek P, Yaspo ML, Della Valle V, Bernard O, Tomassi S, Novellino E, Feoli A, Sbardella G, Gut I, Vellenga E, Stunnenberg HG, Mai A, Martens JHA, Altucci L * Combined HAT/EZH2 modulation leads to cancer-selective cell death(284 views) Oncotarget (ISSN: 1949-2553electronic, 1949-2553linking), 2018 May 22; 9(39): 25630-25646. Impact Factor:5.008 ViewExport to BibTeXExport to EndNote