Chemical biology of Peptide Regulation of Opioid Receptor Function

阿片受体功能肽调节的化学生物学

基本信息

批准号：
10578830
负责人：
Carrie Haskell-Luevano
金额：
$ 63.05万
依托单位：
UNIVERSITY OF MINNESOTA
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-05-01 至 2025-02-28
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10578830
关键词：
Address Adverse effects Affinity Agonist Amino Acids Analgesics Aspirin Basic Science Binding Biology Bypass Chemicals Clinical Communities Complex Constipation DNA sequencing Data Development Disease Drug Design Drug abuse Esthesia European G-Protein-Coupled Receptors GTP-Binding Proteins Goals Heroin Human In Vitro Individual Knowledge Ligands Molecular Molecular Probes Molecular Target Morphine N-terminal Nausea Opioid Opioid Peptide Opioid Receptor Outcome Pain Pain Research Pain management Pathway interactions Peptides Pharmaceutical Chemistry Pharmaceutical Preparations Pharmacology Physiological Population Predisposition Proteins Receptor Activation Regulation Research Research Project Grants Role Sedation procedure Signal Transduction Single Nucleotide Polymorphism Structure Tertiary Protein Structure Test Result Therapeutic Therapeutic Agents Ventilatory Depression addiction antagonist beta-arrestin design drug discovery endogenous opioids evidence base in vivo in vivo evaluation mu opioid receptors novel novel therapeutics pain perception painful neuropathy peptide A pharmacologic protein aminoacid sequence receptor receptor function recruit response side effect standard of care therapeutic development tool

项目摘要

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.

疼痛是每个人在其一生中的某个时刻所经历的一种感觉，导致疼痛的原因不同，因此需要使用阿司匹林和吗啡等药物进行治疗，因为目前的治疗标准是将阿片受体作为其“作用点”。不幸的是，长期治疗疼痛的作用机制。吗啡会引起许多副作用，例如成瘾、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，发现治疗疼痛且副作用最小的新分子靶标，以及这一发现。和新疗法的开发减轻疼痛的药物是全世界科学界不断努力的目标，该研究项目的目标是将未开发的人类阿片受体 N 末端结构域肽描述为治疗疼痛的新化学型，以及它们如何发挥作用。调节阿片受体药理学的影响。药物化学和疼痛研究领域的研究可以推进基于阿片肽的治疗、基于 GPCR 的治疗的配体设计策略的现有范例，并提供新的工具来探索疼痛管理的分子机制。