PAF-receptor. III. Conformational and electronic properties of PAF-like agonists and antagonists.
In order to compare electronic and conformational properties of PAF-agonists and PAF-antagonists, 14 analogues structurally related to PAF were studied. A common conformation of the glycerol backbone was present in all agonists and all constrained or flexible antagonists. The distinction between agonists and antagonists appears to be casted on position-2 where the folded conformation of the substituent for agonists should be the most probable. In position-3 the gauche conformation can be adopted by all the analysed compounds. The electrostatic potential well at -30 kcal/mol stretches to the carbonyl group in position-2 in the folded conformation of the agonists. On the contrary, in constrained antagonists, a second negative zone appears around the carbamate group. Given the modelling results, the triethylammonium PAF analogue considered in literature as a weak agonist, was resynthesized and proved to be more potent than previously reported. These experimental results confirm our hypothesis in terms of a common conformation of agonist and antagonist PAF-like molecules.
Lamotte-Brasseur
J
J
Laboratoire de Microbiologie, Institut de Chimie, Liège, Belgium.
Dive
G
G
Lamouri
A
A
Heymans
F
F
Godfroid
J J
JJ
D004560:Electricity; D004563:Electrochemistry; D008968:Molecular Conformation; D010972:Platelet Activating Factor / Q000031:analogs & derivatives / Q000737:chemistry*; D010974:Platelet Aggregation; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000187:drug effects; D043562:Receptors, G-Protein-Coupled
D010972:Platelet Activating Factor; D010980:Platelet Membrane Glycoproteins; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; C039351:platelet activating factor receptor