Selective Penicillamine Substitution Enables Development of a Potent Analgesic Peptide that Acts through a Non-Opioid-Based Mechanism was written by Gajewiak, Joanna;Christensen, Sean B.;Dowell, Cheryl;Hararah, Fuaad;Fisher, Fernando;Huynh, Peter N.;Olivera, Baldomero M.;McIntosh, J. Michael. And the article was included in Journal of Medicinal Chemistry in 2021.Category: chlorides-buliding-blocks This article mentions the following:
Venom-derived compounds are of broad interest in neuropharmacol. and drug development. α-Conotoxins are small disulfide-containing peptides from Conus snails that target nicotinic acetylcholine receptors (nAChRs) and are in clin. development for non-opioid-based treatment of intractable pain. Although refined by evolution for interaction with target prey receptors, enhancements of pharmacol. properties are needed for use in mammalian systems. Therefore, we synthesized analogs of α-conotoxin RgIA using a combination of selective penicillamine substitutions together with natural and non-natural amino acid replacements. This approach resulted in a peptide with 9000-fold increased potency on the human α9α10 nAChR and improved resistance to disulfide shuffling compared to the native peptide. The lead analog, RgIA-5474, potently blocked α9α10 nAChRs, but not opioid- or other pain-related targets. In addition, RgIA-5474 effectively reversed chemotherapy-induced neuropathic pain. In the experiment, the researchers used many compounds, for example, (Chloromethanetriyl)tribenzene (cas: 76-83-5Category: chlorides-buliding-blocks).
(Chloromethanetriyl)tribenzene (cas: 76-83-5) belongs to organic chlorides. Organochlorines are organic compounds having multiple chlorine atoms. They were the first synthetic pesticides that were used in agriculture. They are resistant to most microbial and chemical degradations. Aliphatic organochlorides are often alkylating agents as chlorine can act as a leaving group, which can result in cellular damage.Category: chlorides-buliding-blocks
Referemce:
Chloride – Wikipedia,
Chlorides – an overview | ScienceDirect Topics