Affinity Labels for Kappa Opioid Receptors

本研究的目的是开发化合物作为研究阿片受体的工具。这些受体是负责麻醉镇痛药（如吗啡）的有益和有害作用的蛋白质。然而，并不是所有的阿片受体都是相同的，这使得这类受体的研究变得复杂。自从15年前发现这些多种阿片受体以来，已经制备了许多化合物，试图区分这些受体类型。使问题进一步复杂化的是，内源性吗啡样物质已从动物体内分离出来。这些化合物，阿片肽，是其他蛋白质的片段，似乎与包括痛觉在内的许多生理功能有关。本研究涉及阿片肽的衍生物之一，啡肽的制备。这种阿片与不同于吗啡受体的kappa-阿片受体相互作用。kappa阿片受体的研究可能会导致更好的非成瘾性镇痛药的开发。合成的阿片类药物含有“亲和标签”，可以使合成的阿片类药物永久地与受体结合。这样，任何神经科学家或药理学家都可以使用这些新肽来区分不同类型的阿片受体。

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.