THE COCAINE RECEPTOR

为了对可卡因受体进行详细研究，我们已经 合作合成并测试了大量的可卡因类似物 和艾薇·卡罗尔博士在RTI。例如，我们发现类似于 也是Win 35,428类似物的可卡因在配基结合方面是有效的 以及在大鼠纹状体组织中的多巴胺运输研究。 这些类似物是已知的最有效的可卡因类似物，其中一些 其效力是可卡因本身的80到100倍。我们还有 合成了~3H-Win 35,065-2并进行了结合研究 是一种有效的可卡因化合物，已被各种 实验室。 这些化合物对结构活性也有很大贡献。 关系信息。我们已经证明了卤素上的取代基 苯环上的C3碳可以增加效力。这些研究已经 对理解可卡因受体的本质的意义 分子的结合区。 我们还在可卡因中使用了不可逆转的结合配体 受体/多巴胺转运体研究大鼠脑内碳水化合物 蛋白质分子。我们的结果表明，碳水合物富含 唾液酸残基，可能与蛋白质N相连。

In order to carry out a detailed study of the cocaine receptor, we have synthesized and tested a large number of cocaine analogs in collaboration with Dr. Ivy Carroll at RTI. For example, we found that analogs of cocaine that are also analogs of WIN 35,428 are potent in ligand binding studies as well as in dopamine transport studies in rat striatal tissue. These analogs are the most potent cocaine analogs known, some of them being 80 to 100 times more potent than cocaine itself. We have also synthesized 3H-WIN 35,065-2 and carried out binding studies because it is a potent cocaine compound that has been studied by a variety of laboratories. These compounds also contribute substantially to structure-activity relationship information. We have shown that halogen substituents on the phenyl ring at the C3 carbon can increase potency. These studies have implications for understanding the nature of the cocaine receptor in the binding region of the molecule. We have also utilized irreversible binding ligands at the cocaine receptor/dopamine transporter to study the carbohydrate moiety of the protein molecule. Our results indicate that the carbyhydrate is rich in sialic acid residues and is probably N-linked to the protein.