Receptors, endocannabinoid conformation

Reggio PH, Traore H (2000) Conformational requirements for endocannabinoid interaction with the cannabinoid receptors, the anandamide transporter and fatty acid amidohydrolase. Chem Phys Lipids 108 15-35... 

Barnett-Norris J, Hurst DP, Lynch DL, Guarnieri F, Makriyannis A, Reggio PH (2002) Conformational memories and the endocannabinoid binding site at the cannabinoid CBI receptor. J Med Chem 45 3649-3659... 

The endocannabinoid acyl chain may need to adopt a folded conformation to interact with CBj, or the endocannabinoid may need to adopt several different conformations in order to reach, be recognized by, and trigger the receptor. Only those analogs with high degrees of eqnihbrinm flexibihty may be able to achieve these conformations easily. 

Acyl chain SAR resnlts also indicate that a minimum of live carbons must be present in the satnrated, terminal region of the acyl chain, and that a minimum of 20 carbons in the acyl chain are reqnired for binding to the catmabinoid CB, receptor. It is difficult to reconcile these requirements based solely on conformational mobility yet any pharmacophore for AEA interaction with CBj shonld be able to accoimt for these two requirements as well. Hypotheses concerning the origin of these two SAR reqnirements are discussed in the section titled Pharmacophore for Endocannabinoid Interaction with Catmabinoid Receptors later in this chapter. 

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