Strategies for the discovery, isolation, and characterization of natural bioactive peptides from the immune system of invertebrates.
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.
Bulet
Philippe
P
TIMC-IMAG, UMR5525 UFF CNRS, Archamps, France.
D000818:Animals; D006458:Hemolymph / Q000737:chemistry; D006801:Humans; D007107:Immune System / Q000737:chemistry*; D007448:Invertebrates / Q000033:anatomy & histology / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism
D010455:Peptides