Lipophilic accessory binding site

These findings suggest that DAR antagonist activity in compounds of the butaclamol series is critically dependent on the presence of a tert-butyl group attached equatorially at position-3 of the nucleus, and furthermore that a lipophilic accessory binding site must exist on the DAR macromolecule, which accommodates the tert-butyl groups of butaclamol, isobutaclamol, anhydrobutaclamol, and, desoxybutaclamol. 

The lipophilic accessory binding site, therefore, is viewed as a uniquely shaped cavity on a membrane surface having a minimum diameter of 2.5 A (Figure 7). Measurements on a model oriented in a cartesian coordinate system calibrated in Angstrom units shows... 

In conclusion, from the study on the relationship between DAR antagonist activity and detailed molecular structure in certain analogs of butaclamol, it has been possible to confirm the existence of a lipophilic accessory binding site on the DAR, to define its probable dimensions, and to specify its locus with respect to the phenyl ring and the nitrogen atom primary binding sites. 

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