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Rational design of novel neurotensin mimetics: Discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist

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Summary

We report the rational design of novel neurotensin mimetics through use of the Multiple Template Approach. This approach is based on our notion that a flexible peptide can be replaced by a partially flexible molecule, identified through testing a comparatively small number of molecules possessing a different intrinsic availability of conformations of the native peptide. The Multiple Template Approach has culminated in the discovery of a pharmacologically unprecedented agent, which behaves as a neurotensin antagonist at low concentration and as a full neurotensin agonist at high concentration.

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Author notes

  1. Javid Zaidi

    Present address: Federal Government College, H-8, Islamabad, Pakistan

  2. Alan P. Kozikowski

    Present address: Trophix Pharmaceuticals, Inc., 89 Headquarters Plaza, North Tower, 14th Floor, 07960, Morristown, NJ, U.S.A.

Authors and Affiliations

  1. Neurochemistry, Mayo Foundation for Medical Education and Research, 4500 San Pablo Road, 32224, Jacksonville, FL, U.S.A.

    Yuan-Ping Pang, Javid Zaidi & Alan P. Kozikowski

  2. Neuropsychopharmacology Research, Mayo Foundation for Medical Education and Research, 4500 San Pablo Road, 32224, Jacksonville, FL, U.S.A.

    Bernadette Cusack & Elliott Richelson

Authors
  1. Yuan-Ping Pang
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  2. Javid Zaidi
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  4. Bernadette Cusack
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  5. Elliott Richelson
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Pang, YP., Zaidi, J., Kozikowski, A.P. et al. Rational design of novel neurotensin mimetics: Discovery of a pharmacologically unprecedented agent exhibiting concentration-dependent dual effects as antagonist and full agonist. J Computer-Aided Mol Des 8, 433–440 (1994). https://doi.org/10.1007/BF00125377

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  • DOI: https://doi.org/10.1007/BF00125377

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