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Download Design and synthesis of small organic molecules as venom antidotes
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Design and synthesis of small organic molecules as venom antidotes Supervisor: Eric Lattmann, Medicinal chemistry Email: [email protected] Venoms are generally peptides acting on various molecular targets. King cobra snake poisons for example work and kill by acting as a “lid like molecule” on the nicotinic acetyl choline receptor. To prevent blockade of the receptor, resulting of death in animals and humans, the only option is to design agents that attack the peptide as target itself. A novel lead structure, isolated from a new curcuma species, a bicyclic functionalised diterpene, will be initially modified by partial synthetic approaches. The synthesis will be guided by molecular modelling studying the docking properties of the peptides and the small organic molecules. The Cache / Argus lab software to be used is fast and reliable to investigate ligand – peptide interactions. The sequence of the neurotoxin B of king cobra toxin is known and based on the optimised 3d peptide structure, docking experiments will be carried out with a novel complex ligand. A design of this lead structure will be systematically performed in order to provide useful molecules for a chemical synthesis. The pharmacophore will be analysed and the structure activity relationships will be fully optimised. Simplified novel molecules and analogues of the lead structures will be prepared by a multistep synthesis. Key words: Partial synthesis, total synthesis, molecular modelling, drug receptor interactions, docking.
