Peptide-Based Drug Design

26 Bulet
bioactive peptides from the innate immune defenses have considerably attracted
the interest of pharmaceutical/biotechnology discovery companies. The isolation
and structural characterization of natural bioactive peptides from the immune
systems of invertebrates can be considered a promising step to discovering
new innovative candidates for development as therapeutics. Although the AMPs
exert relatively lower activities against susceptible microbial strains compared
to conventional low molecular mass antibiotics, they have several advantages
such as a fast target killing, a large activity spectrum, limited toxicity, and a
limited tendency for developing resistance in the target microorganisms (35).
The constant and rising need for innovative therapeutic approaches combined
with the potential of peptides, as active pharmaceutical component for effective
drug formulation, is an important factor in the rapid development of the peptide
market. Throughout our organism, peptides are active regulators and information
brokers that make them interesting for drug development. Peptides have several
virtues compared to the classical small molecules. They show higher specificity,
have few toxicology problems, can be more potent, and do not accumulate in
organs or face drug–drug interactions. Nevertheless, they have some drawbacks.
Peptides are bigger and therefore more expensive to manufacture, and they
may be less stable than chemical drugs, requiring an improved formulation.
However, with recent manufacturing improvements (transgenic expression,
recombinant or synthetic methods) and the development of highly powerful
delivery protocols and techniques to improve stability, the global market for
peptide-based therapeutics is expected to considerably expand. The various
methodologies described here were successful for the characterization of natural
bioactive immune-induced peptides from invertebrates. Depending on the objectives
of the research and of the biological model investigated, the complete panel
of approaches reported in this chapter should be considered together with their
specific limitations.
Acknowledgments
I would like to thank Professors Laurence Ehret-Sabatier (Institut Pluridisciplinaire
Hubert Curien, Strasbourg, France) and Sirlei Daffre (São Paulo
University, Brazil) for critical reading of the manuscript.
References
1. Zhang, L., and Falla, T.J. (2006) Antimicrobial peptides: therapeutic potential.
Expert Opin. Pharmacother. 7(6), 653–663.
2. 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.