Diselenium, instead of disulfide, bonded analogs of conotoxins: novel synthesis and pharmacotherapeutic potential.
The venoms of the cone snail (Conus) contain toxic peptides (conotoxins) that have remarkable selectivity for subtypes of a variety of mammalian voltage- and ligand-gated ion channels, G protein-coupled receptors, and neurotransmitter transporters. They thus have tremendous potential as pharmacologic tools. Less toxic analogs or mimetics could be highly-selective pharmacotherapeutic agents at their target sites. For this reason, conopeptides have been extensively studied and have progressed to clinical trials and even regulatory approval. However, the synthesis of the peptides remains difficult and stability and toxicity remain problems. A novel synthesis and testing of analogs incorporating diselenium bonds between selenocysteine residues in place of disulfide bonds between cysteine residues has recently been reported. The technique results in analogs that retain the folding of the native peptides, are more potent, and have the same or greater biological activity.
Raffa
Robert B
RB
Department of Pharmaceutical Sciences, Temple University School of Pharmacy, Philadelphia, PA 19140, USA. robert.raffa@temple.edu
D000818:Animals; D020916:Conotoxins / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D052078:Conus Snail; D016503:Drug Delivery Systems; D004355:Drug Stability; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000378:metabolism; D017510:Protein Folding; D012643:Selenium / Q000737:chemistry*; D017279:Selenocysteine / Q000737:chemistry
D020916:Conotoxins; D007473:Ion Channels; D017279:Selenocysteine; D012643:Selenium