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Conformational studies on (+)-anatoxin-a and derivatives

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Summary

Anatoxin-a (AnTX) is a highly potent agonist acting at the nicotinic acetylcholine receptor (nAChR) and represents a valuable tool in the study of this receptor. Molecular mechanics, semi-empirical and ab initio molecular orbital energy minimization procedures were conducted to investigate the conformation of AnTX. For each minimization procedure, the s-trans enone isomer of protonated AnTX was the energetically favoured conformer due to intramolecular electrostatic interactions. Our studies are discussed in the light of previous experimental observations and conformational studies, in addition to their importance in the development of future pharmacophore models for nAChR agonist binding.

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Authors and Affiliations

  1. School of Chemistry, Bath University, BA2 7 AY, Bath, Avon, U.K.

    Philip E. Thompson & Timothy Gallagher

  2. Smith Kline Beecham Pharmaceuticals, The Frythe, AL6 9AR, Welwyn, Hertfordshire, U.K.

    David T. Manallack

  3. Smith Kline Beecham Pharmaceuticals, Coldharbour Road, The Pinnacles, CM19 5AD, Harlow, Essex, U.K.

    Frank E. Blaney

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  1. Philip E. Thompson
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  2. David T. Manallack
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  3. Frank E. Blaney
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  4. Timothy Gallagher
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Thompson, P.E., Manallack, D.T., Blaney, F.E. et al. Conformational studies on (+)-anatoxin-a and derivatives. J Computer-Aided Mol Des 6, 287–298 (1992). https://doi.org/10.1007/BF00123382

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  • DOI: https://doi.org/10.1007/BF00123382

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