Summary
Intensive research efforts for developing new anti-infectious drugs for human health rely mostly on technological advancements in high-throughput screening of combinatorial chemical libraries and/or natural libraries generated from animal/plant extracts. However, nature has done a fascinating job engineering its own mutational program through evolution. This results in an incredible diversity of natural bioactive molecules that may represent a starting matrix for developing new generations of therapeutics of commercial promise to control infectious diseases. Among the natural bioactive molecules, peptides are opening promising perspectives. The search for novel bioactive peptides for therapeutic development relies mainly on a conventional approach driven by a desired biological activity followed by the purification and structural characterization of the bioactive molecule. Nevertheless, this strategy requires large quantities of biological material for activity screening and is thus restrained to animal species of large size or that are widely distributed.
During the past 10 years, thanks to the technological improvements of mass spectro-metry (MS) and liquid chromatography, highly sensitive approaches have been developed and integrated into the drug-discovery process. We have used several of these sensitive biochemical technologies to isolate and characterize defense/immune peptides from tiny invertebrates (essentially arthropods) and to limit investigations on a restricted number of individuals. These defense/immune peptides, which are mostly cationic molecules with a molecular mass often below 10 kDa, are the natural armamentarium of the living organisms, and they represent good starting matrices for optimization prior their development as future anti-infectious therapeutics.
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References
Zhang, L., and Falla, T.J. (2006) Antimicrobial peptides: therapeutic potential. Expert Opin. Pharmacother. 7(6), 653–663.
Hancock, R.E., and Sahl, H.G. (2006) Antimicrobial and host-defense peptides as new anti-infective therapeutic strategies. Nat. Biotechnol. 24(12), 1551–1557.
Pereira, H.A. (2006) Novel therapies based on cationic antimicrobial peptides. Curr. Pharm. Biotechnol. 7(4), 229–234.
McPhee, J.B., and Hancock, R.E. (2005) Function and therapeutic potential of host defence peptides. J. Pept. Sci. 11(11), 677–687.
Riley, M.A., and Wertz, J.E. (2002) Bacteriocin diversity: ecological and evolutionary perspectives. Biochimie 84(5–6), 357–364.
Guder, A., Wiedemann, I., and Sahl, H.G. (2000) Posttranslationally modified bacteriocins—the lantibiotics. Biopolymers 55, 62–73.
Jenssen, H., Hamill, P., and Hancock, R.E. (2006) Peptide antimicrobial agents. Clin. Microbiol. Rev. 19(3), 491–511.
Castro, M.S., and Fontes, W. (2005) Plant defense and antimicrobial peptides. Protein Pept. Lett. 12(1), 13–18.
Bulet, P., Stöcklin, R., and Menin, L. (2004) Anti-microbial peptides: from invertebrates to vertebrates. Immunol. Rev. 198, 169–184.
Sitaram, N., and Nagaraj, R. (2002) Host-defense antimicrobial peptides: importance of structure and activity. Curr. Pharm. Des. 8(9), 727–742.
Beisswenger, C., and Bals, R. (2005) Functions of antimicrobial peptides in host defense and immunity. Curr. Protein Pept. Sci. 6(3), 255–264.
Hancock, R.E., Brown, K.L., and Mookherjee, N. (2006) Host defence peptides from invertebrates—emerging antimicrobial strategies. Immunobiology 211(4), 315–322.
Bachère, E., Gueguen, Y., Gonzalez, M., de Lorgeril, J., Garnier, J., and Romestand, B. (2004) Insights into the anti-microbial defense of marine invertebrates: the penaeid shrimps and the oyster Crassostrea gigas. Immunol. Rev. 198, 149–168.
Imler, J.L., and Bulet, P. (2005) Antimicrobial peptides in Drosophila: structures, activities and gene regulation. Chem. Immunol. Allergy 86, 1–21.
Bulet, P., and Stöcklin, R.(2005) Insect antimicrobial peptides: structures, properties and gene regulation. Protein Pept. Lett. 12(1), 3–11.
Lemaitre, B., and Hoffmann, J. (2007) The host defense of Drosophila melanogaster. Annu. Rev. Immunol. 25, 697–743.
Boulanger, N., Munks, R.J., Hamilton, J.V., et al. (2002) Epithelial innate immunity. A novel antimicrobial peptide with antiparasitic activity in the blood-sucking insect Stomoxys calcitrans. J. Biol. Chem. 277(51), 49921–49926.
Kuhn-Nentwig, L. (2003) Antimicrobial and cytolytic peptides of venomous arthropods. Cell Mol. Life Sci. 60(12), 2651–2668.
Uttenweiler-Joseph, S., Moniatte, M., Lagueux, M., Van Dorsselaer, A., Hoffmann, J.A., and Bulet, P. (1998) Differential display of peptides induced during the immune response of Drosophila: a matrix-assisted laser desorption ionization time-of-flight mass spectrometry study. Proc. Natl. Acad. Sci. USA 95(19),11342–11347.
Levy, F., Rabel, D., Charlet, M., Bulet, P., Hoffmann, J.A., and Ehret-Sabatier, L. (2004) Peptidomic and proteomic analyses of the systemic immune response of Drosophila. Biochimie 86(9–10), 607–616.
Chernysh, S., Kim, S.I., Bekker, G., et al. (2002) Antiviral and antitumoral peptides from insects. Proc. Natl. Acad. Sci. USA 99(20), 12628–12632.
Hetru, C., Bulet, P. (1997) Strategies for the isolation and characterization of antimicrobial peptides of invertebrates, in Antimicrobial Peptide Protocols (Shafer, W.M., ed.), Humana Press, Totowa, NJ, pp. 35–49.
Boulanger, N., Ehret-Sabatier, L., Brun, R., Zachary, D., Bulet, P., and Imler, J.L. (2001) Immune response of Drosophila melanogaster to infection with the flagellate parasite Crithidia spp. Insect Biochem. Mol. Biol. 31, 129–137.
Boulanger, N., Lowenberger, C., Volf, P., et al. (2004) Characterization of a defensin from the sand fly Phlebotomus duboscqi induced by challenge with bacteria or the protozoan parasite Leishmania major. Infect. Immun. 72(12), 7140–7146.
Favreau, P., Menin, L., Michalet, S., et al. (2006) Mass spectrometry strategies for venom mapping and peptide sequencing from crude venoms: case applications with single arthropod specimen. Toxicon 47, 676–687.
Bulet, P., and Uttenweiler-Joseph, S. (2000) A MALDI-TOF mass spectrometry approach to investigate the defense reactions in Drosophila melanogaster, an insect model for the study of innate immunity, in RM Kamp, D Kyriakidis, Th Choli-Papadopoulos, ed. Springer Proteome and Protein Analysis (Kamp, R.M., Kyriakidis, D., and Choli-Papadopoulos, T., eds.), Springer-Verlag, Berlin, pp. 157–174.
Carte, N., Cavusoglu, N., Leize, E., Van Dorsselaer, A., Charlet, M., and Bulet, P. (2001) De novo sequencing by nano-electrospray multiple-stage tandem mass spectrometry of an immune-induced peptide of Drosophila melanogaster. Eur. J. Mass Spectrom. 7(4), 399–408.
Favreau, P., Cheneval, O., Menin, L., et al. (2007) The venom of the snake genus Atheris contains a new class of peptides with clusters of histidine and gylcine residues. Rapid Commun. Mass Spectrom. 21(3), 406–412.
Destoumieux, D., Munoz, M., Cosseau, C., et al. (2000) Penaeidins, antimicrobial peptides with chitin-binding activity, are produced and stored in shrimp granulocytes and released after microbial challenge. J. Cell Sci. 113, 461–469.
Rabel, D., Charlet, M., Ehret-Sabatier, L., et al. (2004) Primary structure and in vitro antibacterial properties of the Drosophila melanogaster attacin C pro-domain. J. Biol. Chem. 279(15), 14853–14859.
Boulanger, N., Munks, R.J.L., Hamilton, J.V., et al. (2002) Epithelial innate immunity. A novel antimicrobial peptide with antiparasitic activity in the blood-sucking insect Stomoxys calcitrans. J. Biol. Chem. 32(4), 369–375.
Vizioli, J., Richman, A.M., Uttenweiler-Joseph, S., Blass, C., and Bulet, P. (2001) The defensin of the malaria vector mosquito Anopheles gambiae: antimicrobial activities and expression in adult mosquitoes. Insect Biochem. Mol. Biol. 31,241–248.
Lamberty, M., Zachary, D., Lanot, R., et al. (2001) Insect immunity. Constitutive expression of a cysteine-rich antifungal and a linear antibacterial peptide in a termite insect. J. Biol. Chem. 276(6), 4085–4092.
Royet, J., Reichhart, J.M., and Hoffmann, J.A. (2005) Sensing and signaling during infection in Drosophila. Curr. Opin. Immunol. 17, 11–17.
Marr, A.K., Gooderham, W.J., and Hancock, R.E. (2006) Antibacterial peptides for therapeutic use: obstacles and realistic outlook. Curr. Opin. Pharmacol. 6(5),468–472.
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Bulet, P. (2008). Strategies for the Discovery, Isolation, and Characterization of Natural Bioactive Peptides from the Immune System of Invertebrates. In: Otvos, L. (eds) Peptide-Based Drug Design. Methods In Molecular Biology™, vol 494. Humana Press. https://doi.org/10.1007/978-1-59745-419-3_2
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DOI: https://doi.org/10.1007/978-1-59745-419-3_2
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