OPIOID PEPTIDE ANALOGS AS PROBES OF OPIOID RECEPTORS

描述：（申请人摘要） 本申请是独立科学家奖（K 02）的申请， 简·奥尔德里奇博士在药物滥用领域的研究。 博士 奥尔德里奇的长期目标是使用化学方法来研究 生物学上重要的蛋白质和它们的配体之间的相互作用。 的 她的主要研究重点一直是并将继续在该领域 阿片肽 这项研究计划的长期目标是利用 阿片肽作为工具，以更好地了解 这些化合物与阿片受体的相互作用，并设计新的 阿片受体的肽和拟肽配体。 本研究 目前主要有两个项目。 一个项目的重点是综合 阿片受体的基于肽的亲和标记物及其用途 研究阿片受体结构和受体-配体的共价配体 交互. 第二个项目涉及探索结构， 肽的构象和形貌要求，特别是 强啡肽衍生物，用于与κ阿片受体相互作用。 一个独立的科学家奖将允许奥尔德里奇博士扩大她的 她在阿片肽研究相关领域的专业知识。 的一部分 这个奖项，她将获得经验，在几个领域，特别是使用 阿片受体的计算模型，以检查可能的受体-配体 相互作用和设计新的阿片配体;应用分析 技术，特别是质谱，来研究配体-受体 相互作用;使用组合方法设计新型配体 阿片受体;并将蛋白质分离技术应用于阿片类药物 受体。 为了获得这些领域的经验，她将与 博士西蒙（纽约大学医学中心）以及与她 马里兰州大学的同事。 这些领域的经验将 补充她在肽化学方面的专业知识，并将提高她的能力， 为药物滥用领域的研究作出贡献。

DESCRIPTION: (Applicant's Abstract) This application is a request for an Independent Scientist Award (K02) to further Dr. Jane Aldrich's research in the area of drug abuse. Dr. Aldrich's long term goals are to use chemical approaches to study interactions between biologically important proteins and their ligands. The main focus of her research has been and will continue to be in the area of opioid peptides. The long term goals of this research program are to use opioid peptides as tools to obtain a better understanding of the interactions of these compounds with opioid receptors and to design new peptide and peptidomimetic ligands for opioid receptors. This research currently involves two major projects. One project focuses on the synthesis of peptide-based affinity labels for opioid receptors and the use of these covalent ligands to study opioid receptor structure and receptor-ligand interactions. The second project involves exploring the structural, conformational and topographical requirements for peptides, specifically dynorphin derivatives, for interaction with kappa opioid receptors. An Independent Scientist Award will allow Dr. Aldrich to expand her expertise in areas related to her research on opioid peptides. As part of this award she will gain experience in several areas, specifically using computational models of opioid receptors to examine possible receptor-ligand interactions and to design new opioid ligands; applying analytical techniques, specifically mass spectrometry, to studying ligand-receptor interactions; using combinatorial approaches to the design of novel ligands for opioid receptors; and applying protein isolation techniques to opioid receptors. In order to gain experience in these areas she will work with Dr. Simon (New York University Medical Center) as well as with her colleagues at the University of Maryland. Experience in these areas will complement her expertise in peptide chemistry and will enhance her ability to contribute to research in the area of drug abuse.