Antimicrobial peptides discovery

Sperstad, S. V., Haug, T., Blencke, H. M., Styrvol, . B., Li, C, and Stensvag, K. (2011). Antimicrobial peptides from marine invertebrates Challengers and perspectives in marine antimicrobial peptide discovery. Biotechnol. Adv. 29, 519-530. 

G. Wang, Structural Studies of Antimicrobial Peptides Provide Insight into Their Mechanisms of Action , in Advances in Molecular and Cellular Microbiology, ed. G. Wang, CAB International, 2010, Vol. 18, Antimicrobial Peptides Discovery, Design and Novel Therapeutic Strategies, p. 141. 

Key Words Invertebrate immunity antimicrobial peptides immune effectors mass spectrometry drug discovery Drosophila arthropods peptide purification molecular mass fingerprints bioactive peptides. 

A QSAR seeks to relate quantitative properties (descriptors) of a compound with other properties such as drug-like activity or toxicity. The essential assumption of QSAR is that quantities that can be conveniently measured or calculated for a compound can be used to accurately predict another property of interest (e.g., antibacterial activity) in a nontrivial way. QSAR has become an integral part of screening programs in pharmaceutical drug-discovery pipelines of small compounds and more recently in toxicological studies (69). However, the use of QSAR modeling applied to the search for antimicrobial peptides is relatively recent. Advances in this area are reviewed in brief here. 

ZHANG YA, zou J, CHANG Cl, SECOMBES cj (2004), Discovery and characterization of two types of liver-expressed antimicrobial peptides 2 (LEAP-2) genes in rainbow trout , Vet Immunol Immunopathol, 101, 259-69. 

Discovery and characterization of two isoforms of moronecidin, a novel antimicrobial peptide from hybrid striped bass. / Biol Chem 2002 Feb 15 277(7) 5030-9. 

In retrospect, neither of these important antimicrobial agents could have been developed if Lilly did not have a fully integrated natural products discovery group that included scientists dedicated to bioconversions of natural products and medicinal chemists dedicated to modifying complex cyclic peptides and other secondary metabolites. This may be a lesson learned to help guide antibiotic discovery and development in the 21st century. 

As mentioned in the introduction to this chapter, the recent discovery of thiolactone peptides as potential antimicrobial agents, based on flieir ability to act as antagonists of natural auto-inducing peptides (AIP), prompted the new synthetic achievements, which permitted the synthesis of these cyclic peptide inhibitors. Here, we discuss the most recent achievement in the synthesis of AIP mimics, based on an original linker for the Fmoc-based solid-phase methodology. 

There are two main reasons for the continued discovery of new AMPs first, new AMPs keep being discovered from different sources, of which the animal kingdom is an extremely important one. A large number of animal species, including insects, produce peptides that have antimicrobial properties (Andreu and Rivas, 1998 Brogden et al, 2003 Zasloff, 2002). 

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