OPIOID PEPTIDE ANALOGS AS PROBES OF OPIOID RECEPTORS

描述：(申请人摘要) 本申请书要求颁发独立科学家奖(K02)，以 简·奥尔德里奇博士在药物滥用领域的进一步研究。Dr。 奥尔德里奇的长期目标是使用化学方法来研究 生物重要蛋白质与其配体之间的相互作用。这个 她的主要研究重点一直是并将继续在以下领域 阿片肽。这项研究计划的长期目标是利用 阿片肽作为工具来更好地了解 这些化合物与阿片受体的相互作用并设计新的 阿片受体的多肽和模拟多肽配体。这项研究 目前涉及两个主要项目。其中一个项目的重点是合成 阿片受体的基于多肽的亲和标记及其用途 研究阿片受体结构和受体-配体的共价配体 互动。第二个项目涉及探索结构， 对多肽的构象和地形要求，特别是 强啡肽衍生物，用于与kappa阿片受体相互作用。 独立科学家奖将允许奥尔德里奇博士扩大她的 在与她的阿片肽研究相关的领域拥有专业知识。作为以下内容的一部分 这个奖项她将在几个领域获得经验，特别是使用 阿片受体的计算模型以检测可能的受体-配体 相互作用和设计新的阿片配体；应用分析 研究配体-受体的技术，特别是质谱学 相互作用；使用组合方法设计新的配体 阿片受体；以及将蛋白质分离技术应用于阿片类药物 感受器。为了获得这些领域的经验，她将与 西蒙博士(纽约大学医学中心)以及她 马里兰大学的同事们。在这些领域的经验将 补充她在多肽化学方面的专业知识，并将增强她的能力 对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.