Affinity Labels for Kappa Opioid Receptors

Kappa 阿片受体的亲和力标签

• 批准号: 9023149
• 负责人: Thomas Murray
• 金额: $ 19.37万
• 依托单位: Oregon State University
• 依托单位国家: 美国
• 项目类别: Continuing Grant
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-03-15 至 1995-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=9023149&HistoricalAwards=false
• 关键词: Affinity; Labels; Kappa; Opioid; Receptors

The purpose of this research is to develop compounds as tools to study opioid receptors. These receptors are proteins which are responsible for both the beneficial and the undisirable effects of narcotic analgesics such as morphine. However, not all opioid receptors are identical and this has complicated the study of this receptor group. Since the demonstration of these multiple opioid receptors about fifteen years ago, numerous compounds have been prepared in attempts to differentiate the receptor types. To further complicate the issue, endogenous morphine-like substances have been isolated from animals. These compounds, opioid peptides, are fragments of other proteins and appear to be involved in a number of physiological functions including pain sensation. This research involves the preparation of derivatives of one of the opioid peptides, dynorphin. This opioid interacts with kappa-opioid receptors which are distinct from morphine receptors. The study of kappa opioid receptors may lead to the development of better nonaddictive analgesics. The opioids are synthesized containing 'affinity labels' which cause the synthetic opioid to permanently bind to the receptor. In this way, any neuroscientists or pharmacologist may use these new peptides to differentiate between the various types of opioid receptors.

这项研究的目的是开发化合物作为研究阿片受体的工具。这些受体是一种蛋白质，负责吗啡等麻醉性镇痛剂的有益和不可消除的效果。然而，并不是所有的阿片受体都是相同的，这使得对这一受体组的研究变得复杂。自从大约15年前证实了这些多个阿片受体以来，人们已经制备了许多化合物来尝试区分受体类型。使问题进一步复杂化的是，从动物身上分离出了内源性吗啡类物质。这些化合物，阿片肽，是其他蛋白质的片段，似乎参与了许多生理功能，包括痛感。这项研究涉及阿片肽之一强啡肽的衍生物的制备。这种阿片类药物与不同于吗啡受体的kappa-阿片受体相互作用。对kappa阿片受体的研究可能会导致更好的非成瘾止痛药的开发。阿片类药物是合成的，含有使合成的阿片类药物永久结合到受体上的“亲和标记”。通过这种方式，任何神经学家或药理学家都可以使用这些新的多肽来区分不同类型的阿片受体。