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：
10348174
负责人：
Carrie Haskell-Luevano
金额：
$ 63.83万
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/10348174
关键词：
Address Adverse effects Affinity Agonist Amino Acids Analgesics Aspirin Basic Science Binding Biology Bypass Chemicals Clinical Communities Complex Constipation Crystallization DNA sequencing Data Development Disease Drug Design Drug abuse Esthesia European G-Protein-Coupled Receptors GTP-Binding Protein alpha Subunits, Gs GTP-Binding Proteins Goals Heroin Human In Vitro Individual Knowledge Lead Ligands Molecular Molecular Mechanisms of Action 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 base 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 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.

痛苦是每个人在生活中的某个时刻所实现的一种感觉。疼痛的不同原因导致通过服用从阿司匹林到吗啡作为当前护理标准的药物治疗。吗啡将阿片类受体作为其“靶向”作用机理。不幸的是，长期治疗疼痛吗啡会引起许多不利影响，例如成瘾，耐受性，恶心，镇静，呼吸抑郁，便秘等。这是理解疼痛感知的不同机制，发现新的分子靶标，以最小的不希望的副作用治疗疼痛，以及发现和开发新疗法。减轻痛苦的代理是全世界科学界的努力。该研究项目的目的是表征意外的人类阿片类受体N末端结构域肽是治疗疼痛及其调节阿片类药物药理学的新化学型。预期结果的影响关于医学化学和疼痛研究领域，可以推动基于阿片类肽的治疗，基于GPCR的治疗的配体设计策略的现有范式，并提供新的工具来探测疼痛管理的分子机制。