Chemical biology of Peptide Regulation of Opioid Receptor Function

痛苦是每个人在他或她的生命中的某个时刻所意识到的一种感觉。不同的疼痛原因导致了从阿司匹林到吗啡等药物的治疗，这是目前的治疗标准。吗啡以阿片受体为靶标，作为其“靶向”作用机制。不幸的是，延长疼痛的治疗时间 吗啡会引起许多不良反应，如上瘾、耐受、恶心、镇静、呼吸抑制、便秘等。因此，了解疼痛感知的不同机制，发现新的分子靶点，以最小的不良副作用治疗疼痛，以及新的治疗方法的发现和发展 止痛剂是全世界科学界正在进行的一项努力。本研究的目的是表征未被发现的人类阿片受体N-端多肽作为一种新的治疗疼痛的化学类型，以及它们如何调节阿片受体的药理学。预期结果的影响 在药物化学和疼痛研究领域的研究可以推进现有的阿片肽类药物和gpr类药物的配基设计策略，并为探索疼痛控制的分子机制提供新的工具。

Pain is a sensation realized by every individual at some point in his or her lives. Different causes of pain result in treatment by administration of drugs ranging from aspirin to morphine as the current standard of care. Morphine targets the opioid receptors as its “on-target” mechanism of action. Unfortunately, prolonged treatment of pain with morphine causes many adverse effects such as addiction, tolerance, nausea, sedation, respiratory depression, constipation, and others. Thus, understanding the different mechanisms for pain perception, discovery of new molecular targets to treat pain with minimal undesired side effects, and the discovery and development of new therapeutic agents for the alleviation of pain is an on going effort by the scientific community world- wide. The goal of this research project is to characterize the unexplored human opioid receptor N-terminal domain peptides as a new chemotype for the treatment of pain and how they modulate opioid receptor pharmacology. The impact of the anticipated results on the medicinal chemistry and pain research fields could advance the existing paradigms for ligand design strategies for opioid peptide based therapeutics, GPCR based therapeutics, as well as provide novel tools to probe the molecular mechanisms of pain management.