Receptors stereochemistry

Korach KS, Levy LA, Sarver PJ. Estrogen receptor stereochemistry Receptor binding and hormonal responses. J Steroid Biochem 1987 27 281-90. 

Johansen, T. N Janin, Y. L Nielsen, B Frydenvang, K., Brauner-Osbome, H., Stensb0l, T. B et al. (2002) 2-Amino-3-(3-hydroxy-l,2,5-thiadiazol-4-yl)propionic acid resolution, absolute stereochemistry and enantiopharmacology at glutamate receptors. Bioorg. Med. Chem. 10, 2259-2266. 

Ebert, B Lenz, S. M Brehm, L Bregnedal, P Hansen, J. J., Frederiksen, K., et al. (1994) Resolution, absolute stereochemistry, and pharmacology of the S -(+)- and R-(-)-isomers of the apparent partial AMPA receptor agonist (R,5)-2-amino-3-(3-hydroxy-5-phcnylisoxazol-... 

Both U-62066 (spiradoline) (10) and PD 117302 (12) are racemic mixtures of two enantiomers. The kappa opioid activity has been shown to reside in the (—) enantiomer, and in the case of U62066 the (-h) enantiomer is a weak mu receptor agonist [49, 50]. (See above for discussion on absolute stereochemistry.)... 

Dynamic combinatorial chemistry (DCC) is marvelously effective at discovering receptors for a broad array of analytes. The nature of the internal competition experiment ensures (normally) that the most effective binder for the analyte of interest is amplified for subsequent identification and characterization. In the context of a host-guest assembly, the issue of stereochemistry can be manifested in a number of scenarios. These include various permutations of chiral or achiral guests, along with achiral, enan-tiopure, or racemic dynamic library components. 

From the viewpoint of stereochemistry, Sections 5.2-5.4 focus on the templated/amplified components of the DCL itself, with the emphasis on how diastereomeric receptors differentially respond to the host-guest assay. Spectacular structures have emerged from the internal competition for the best binder(s) to an analyte. 

The stereochemistry of the y-isomer is shown in the diagram, and when converted into a conformational stereodrawing it can be seen that there are three axial chlorines and three equatorial ones. Ring flip produces an alternative conformation of equal energy, but it can be seen that this is identical to the first stracture rotation through 180° produces an identical and, therefore, superimposable structure. It can be seen that conformational change will not stop the compound interacting with the insect receptor site. 

X-ray structural data are available for TPA (35) and dihydro-teleocidin B (36-37), but only the absolute stereochemistry of TPA is known. As mentioned above the structure of aplysiatoxin has been solved by X-ray crystallography and its absolute stereochemistry has been determined from other data (10). These three tumor promoters, which represent three distinct classes of natural products, appear to have common structural features that enable it to bind to the same membrane receptors. 

Three related tetramic acids have been reported from Chaetomium globosum. Two (44, 45) differ in the stereochemistry of the amino acid component, and the third is the methyl ester of 44 [79]. It is claimed that these compounds are chemokine receptor antagonists and can be used to treat HIV-1 infections. 

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