Diastereomers receptor binding

Diastereomeric drugs— those having two or more asymmetric centers—are usually active in only one configuration. Unlike enantiomers, which have identical physicochemical properties, the absorption, distribution, receptor binding, metabolism, and every other aspect that influences the pharmacological activity of a dmg are different for each diastereomer. 

The degeneracy of the non-chiral complexes can be removed by incorporating chiral centers, usually as resolved amino acids, into the arms at close vicinity to the hydroxamate iron binding sites. Thus, only one of the energetically non-equivalent diastereomers predominates, leading to pure enantiomeric iron(III) complexes with defined hehcity that allows assessing stereospecific recognition by the ferrichrome receptor. 

Interestingly, the two diastereomers 18 and 19 are equipotent to All in binding to the ATj receptor. In a functional assay, using contraction of rabbit aorta rings, one of these diastereomers is a full agonist, but has approximately 300-fold less potency that All. Both diastereomers 20 and 21 were devoid of activity. 

Mefloquine 274 is a useful alternative treatment agent for Plasmodium vivax malaria and Plasmodium falciparum malaria in areas, where chloroquine is still recommended as the first-hne therapeutic agent.Mefloquine is a chiral molecule with two asymmetric carbon centers, and it exists as a mixture of diastereomers. The drug is currently manufactured and sold as a racemate of the (+1—) R,S enantiomers by Hoffman-LaRoche. The (+) enantiomer is more effective in treating malaria, and the (—) enantiomer specifically binds to adenosine receptors in the central nervous system, which may explain some of its psychotropic effects.It is not known whether mefloquine can be transformed into its stereoisomer in vivo. 

The affinity differences for the diastereomers of PIA are often used as criteria for adenosine receptor subtype classification. The results summarized in Table III demonstrate that the diastereomeric selectivity for R- and S-PIA at Aj adenosine receptors is remarkably stable in a variety of radioligand binding and physiological assays. The largest difference in affinity was observed in the solubilized porcine atrial Aj adenosine receptor where R-PIA was approximately 43 fold more potent than S-PIA as an inhibitor of [1 I]HPIA binding. 

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