Structural Requirements for Cannabinoid Receptor Probes 233Fig. 19.Covalent probes for cannabinoid receptors
of the various classes of cannabinergics for the CB 1 and CB 2 receptors. This ligand-
based approach in structural biology can serve as a useful avenue for studying the
active sites of membrane-bound structural proteins that are not easily amenable
to a crystallization approach.
4
Enantioselective Cannabinergic Ligands
Ligand enantioselectivity is often an important criterion in the characterization of
drug receptors and in the development of biochemical and pharmacological assays.
Thus, a highly enantioselective enantiomer can be a radioligand in a binding assay
in which its much-less-potent enantiomer can be used to determine non-specific
binding. Similarly, the less active enantiomer can serve as a control in in vitro or
in vivo drug evaluations.
The cannabinergic ligand library includes a number of key enantiomeric pairs
that have found substantial use in laboratories engaged in cannabinoid research.
A careful examination of the literature reveals striking discrepancies in reported
bioenantioselectivities. These are generally attributable to inadequate chiral reso-
lution leading to a chirally impure enantiomer. Variation in enantioselectivity can