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[摘要]：Endocannabinoids are endogenous polyunsatd. fatty acids involved in a multitude of health and disease processes. Recently, several lines of evidence suggest the presence of a novel non-CB1/CB2 anandamide receptor in endothelial cells. Thus, we synthesized two types of photoaffinity probes, e.g. I and II, that contain either an arylazide group or a diazirin moiety, together with a fluorescent analog. The key steps rely on selective hydrogenation of skipped tetrayne backbones and on copper-mediated cross-coupling reactions between diynic precursors. Three synthetic routes were investigated. In biol. functional assays, we found that both the arylazide and the fluorescent probes induced robust increases in matrix metalloprotease activity and produced pos. angiogenic responses in in vitro endothelial cell tube formation assays. Irradn. of the arylazide probe nicely enhanced this effect in both HUVEC and CB1-KO HUVEC. These results suggest that the arylazide and the fluorescent probes can be used to identify "non-CB1/CB2 anandamide receptor" from endothelial cells. |
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