Physico-chemical properties of prostaglandins and related pharmacological compounds. A theoretical study on conformational related activity.
Thromboxane A2, prostaglandin H2, a series of chemically stable cyclic endoperoxide analogues (U 46619, U 44069, ONO 11113, 9, 11, diazo PGH2 and SQ 26655) and different isomers of SQ 26655 were analysed for their spatial configuration by conformational analysis in a simulated membrane-water interface environment with a "structure tree" procedure already described for prostaglandins, leukotrienes and lipoxins. The conformers derived from the structure tree and with a high probability of existence are presented. A new method allows one to visualize the surface charge density of the calculated molecules. The spatial configuration and the surface charge density of each molecule are compared to their known order of competition binding to the putative TXA2/PGH2 receptor of platelets. The conformational and charge density analysis merely shows that the different stereochemistry of these molecules lead to spatial conformation, that mimics (agonists), or that are far from (antagonists) the TXA2/PGH2 conformation.
UCB Pharmaceutical Sector, Braine-l'Alleud, Belgium.
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Brasseur
D055598:Chemical Phenomena; D002627:Chemistry, Physical; D008956:Models, Chemical; D008958:Models, Molecular; D008968:Molecular Conformation; D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D044262:Prostaglandin H2; D011463:Prostaglandins H; D013329:Structure-Activity Relationship; D013928:Thromboxane A2 / Q000031:analogs & derivatives
D011449:Prostaglandin Endoperoxides; D011450:Prostaglandin Endoperoxides, Synthetic; D011463:Prostaglandins H; D044262:Prostaglandin H2; D013928:Thromboxane A2