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PAF receptor structure: A hypothesis

  • PAF Receptor and Antagonists
  • Review
  • Published:
Lipids

Abstract

Different hypotheses of the structure of platelet-activating factor (PAF) receptor based on structure-activity relationships of agonists and antagonists are reviewed. For an agonistic effect, strong hydrophobic interactions and an ether function are required in position-1 of the glycerol backbone; chain length limitations and steric hindrance demand a small group in position-2. The unusual structural properties of non-PAF-like antagonists required 3-D electrostatic potential calculations. This method applied to seven potent antagonists suggests a strong “Cache-oreilles” (ear-muff) effect,i.e., two strong electronegative wells (isocontour at −10 Kcal/mole) are located at 180° to each other and at a relatively constant distance. Initial consideration of the “Cache-oreilles” effect implied the structure of a bipolarized cylinder of 10–12 Å diameter for the receptor. However, very recent results on studies with agonists and antagonists structurally similar to PAF suggest that the receptor may in fact be a multi-polarized cylinder.

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Abbreviations

3-D:

three-dimensional (electrostatic potential map)

PAF:

platelet-activating factor

QSAR:

quantitative structure activity relationship

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Authors and Affiliations

  1. Centre d'Ingéniérie des Protéines, Institut de Chimie, Liège-Sart-Tilman, Belgium

    G. Dive & J. Lamotte-Brasseur

  2. Laboratoire de Pharmacochimie Moléculaire, Université Paris 7, 2, Place Jussieu, 75251, Paris Cedex 05, France

    J. J. Godfroid, J. P. Batt & F. Heymans

Authors
  1. J. J. Godfroid
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  2. G. Dive
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  3. J. Lamotte-Brasseur
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  4. J. P. Batt
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  5. F. Heymans
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Godfroid, J.J., Dive, G., Lamotte-Brasseur, J. et al. PAF receptor structure: A hypothesis. Lipids 26, 1162–1166 (1991). https://doi.org/10.1007/BF02536523

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  • DOI: https://doi.org/10.1007/BF02536523

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