THE COCAINE RECEPTOR

可卡因受体

• 批准号: 3853708
• 负责人: M J KUHAR
• 金额: --
• 依托单位: NATIONAL INSTITUTE ON DRUG ABUSE
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/3853708
• 关键词: analog; chemical binding; chemical structure function; cocaine; dopamine; drug design /synthesis /production; drug receptors; glycoprotein structure; laboratory rat; receptor binding; sialate

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.

为了对可卡因受体进行详细的研究，我们 合成并测试了大量的可卡因类似物 和RTI的艾薇卡罗尔博士一起 例如，我们发现， 也是WIN 35，428类似物的可卡因在配体结合中是有效的 研究以及大鼠纹状体组织中多巴胺转运研究。 这些类似物是已知的最有效的可卡因类似物，其中一些 比可卡因本身的效力强80到100倍。 我们还 合成3 H-WIN 35，065 -2并进行结合研究，因为它 是一种强效的可卡因化合物，已经被各种各样的 laboratories. 这些化合物也对结构活性有很大贡献 关系信息。 我们已经证明， 在C3碳上的苯环可以增加效力。 这些研究 对理解可卡因受体的性质的影响 分子的结合区。 我们还利用了可卡因的不可逆结合配体， 受体/多巴胺转运蛋白研究的碳水化合物部分， 蛋白质分子 我们的研究结果表明，碳水化合物富含 唾液酸残基，可能是N-连接的蛋白质。