Antimicrobial peptides, limitations

The use of QSAR descriptors for prediction and understanding of the activity of antimicrobial peptides has previously been limited to comparisons between peptides that differ in only a small number of amino acids. This has been primarily due to the cost and difficulty of producing large numbers of peptides as well as the cost of assaying their activity. However, with the recent advance in high-throughput peptide synthesis technique in combination with rapid assay of activity with the luminescence-based assay, robust amounts of data have begun to be available (35). 

Abstract Infectious diseases cause severe problems in the aquaculture industry, with viral diseases being responsible for the greatest losses in production. Disease prevention strategies still have some limitations in terms of safety and efficacy. Antimicrobial peptides (AMPs) are molecules of the innate immune system, one of the first lines of defense against pathogens. Usually they not only exhibit antimicrobial activity, but also modulate the immune response. This review focuses on fish AMPs and their antiviral and immunoregulatory activities in order to assess their potential relevance to aquaculture. Since fish depend on their innate immune defenses more than mammals, they could be an alternative source of novel antiviral compounds. 

Recently, the activities of host defense peptides related to the resolution of infection have been suggested to result in part from nondirect antimicrobial activities. It has been postulated that immunomodulation may represent the primary action of these peptides in vivo as the immunomodulatory activities are retained under physiological conditions in contrast to the direct antimicrobial activities of most natural mammalian host defense peptides. These immunomodulatory activities include, but are not limited to, direct chemotactic activity, induction of chemokines and other immune mediators, stimulation of leukocyte degranulation and other microbicidal activities, effects on leukocyte and epithelial cell survival and apoptosis, stimulation of epithelial and endothelial cell proliferation, promotion of wound healing and angiogenesis, antiendotoxic and anti-inflammatory activities, and adjuvant fiinctions. These will be described in detail in the following sections and a summary is found in Table 1. 

While this approach has limitations related to the peptidic nature of the linker such as stability to harsh reaction conditions and requirement of specific functional groups to be coupled with the linker arms, its application to particular libraries and chemistries may be useful. Its biological utility was assessed in a bead-based antimicrobial assay on bacterial cells [54], which produced good correlations between the MIC (minimal inhibitory concentration) values for the compounds released in situ in the culture medium from the beads or tested as standard solutions. 

---