Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity(555 views) Scudiero O, Galdiero S, Cantisani M, Di Noto R, Vitiello M, Galdiero M, Naclerio G, Cassiman JJ, Pedone C, Castaldo G, Salvatore F
CEINGE-Biotecnologie Avanzate, Naples, Italy. salvator@unina.it
Dipartimento di Biochimica e Biotecnologie Mediche, Università di Napoli Federico II, Naples, Italy
Dipartimento di Scienze Biologiche, Sezione di Biostrutture, Università di Napoli Federico II, Naples, Italy
Istituto di Biostrutture e Bioimmagini, CNR, Naples, Italy
Centro Interuniversitario di Ricerca Sui Peptidi Bioattivi, Naples, Italy
Dipartimento di Medicina Sperimentale, Seconda Università di Napoli, Naples, Italy
Facoltà di Scienze, Università del Molise, Isernia, Italy
Center for Human Genetics, University of Leuven, Leuven, Belgium
Scuola Europea di Medicina Molecolare (SEMM), Naples, Italy
IRCCS-Fondazione SDN, Naples, Italy
Clinica Pineta Grande, Castelvolturno, Caserta, Italy
Facolt di Scienze, Universit del Molise, Isernia, Italy
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Sawai, M. V., Jia, H. P., Liu, L., Aseyev, V., Wiencek, J. M., McCray Jr., P. B., Ganz, T., Tack, B. F., The NMR structure of human beta-defensin-2 reveals a novel alpha-helical segment (2001) Biochemistry, 40, pp. 3810-3816
Schibli, D. J., Hunter, H. N., Aseyev, V., Starner, T. D., Wiencek, J. M., McCray Jr., P. B., Tack, B. F., Vogel, H. J., The solution structures of the human beta-defensins lead to a better understanding of the potent bactericidal activity of HBD3 against Staphylococcus aureus (2002) J. Biol. Chem., 277, pp. 8279-8289
Selsted, M. E., Ouellette, A. J., Mammalian defensins in the antimicrobial immune response (2005) Nat. Immunol., 6, pp. 551-557
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Starner, T. D., Agerberth, B., Gudmundsson, G. H., McCray Jr., P. B., Expression and activity of beta-defensins and LL-37 in the developing human lung (2005) J. Immunol., 174, pp. 1608-1615
Wu, Z., Hoover, D. M., Yang, D., Boulegue, C., Santamaria, F., Oppenheim, J. J., Lubkowski, J., Lu, W., Engineering disulfide bridges to dissect antimicrobial and chemotactic activities of human -defensin 3 (2003) Proc. Natl. Acad. Sci. U. S. A., 100, pp. 8880-8885
Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity
Human beta-defensins (hBDs) are antimicrobial peptides of human innate immunity. The antibacterial activities of hBDs 1, 2, and 4 but not the activity of hBD3 are impaired by high salt levels. We have designed and synthesized seven novel hBD analogs, constituted by different domains of hBD1 (which is constitutively expressed in humans) and of hBD3 (which is induced by microorganisms and inflammatory factors in humans), that would maintain and potentially increase the wild-type antimicrobial activities and be salt resistant. We have compared the antibacterial, antiviral, and chemotactic activities of the analogs with those of hBD1 and hBD3. We show that the hBD1 internal region and the hBD3 C-terminal region are critical for antibacterial activity also at high salt concentrations, whereas deletion of the N-terminal region of hBD3 results in an increase in antibacterial activity. All analogs inhibited herpes simplex virus; antiviral activity was enhanced by the hBD1 internal region and the hBD3 C-terminal region. Wild-type and analog peptides were chemotactic for granulocytes and monocytes, irrespective of the salt concentrations. These new peptides may have therapeutic potential.
Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity
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Novel synthetic, salt-resistant analogs of human beta-defensins 1 and 3 endowed with enhanced antimicrobial activity