Opioid Peptide Analogs as Probes of Opioid Receptors

描述(由申请人提供)： 这项申请是对独立科学家奖(K02)的竞争性更新，以促进简·奥尔德里奇博士在药物滥用领域的研究。奥尔德里奇博士的长期目标是设计和使用新的阿片肽和类肽配体作为药理学工具，以更好地了解阿片肽-受体的相互作用。这项拟议的研究结合了化学、药理学和计算技术，其基本原理是，从这些免费的方法中获得的信息将限制多肽与受体残基相互作用的可能性，从而极大地促进阿片受体结合多肽模型的开发。 独立科学家奖的延续将使奥尔德里奇博士能够在与她的阿片肽研究相关的几个领域扩大她的专业知识。这些领域包括合成(包括立体选择性合成)新的氨基酸类似物以并入阿片肽类似物，熟悉研究阿片受体的分子生物学技术，以及获得更多通过质谱学表征蛋白质的经验。这些领域的经验将与奥尔德里奇博士在多肽化学方面的专业知识相结合，大大增强她对药物滥用领域研究的贡献。

DESCRIPTION (provided by applicant): This application is a competitive renewal of 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 design and use new opioid peptide and peptidomimetic ligands as pharmacological tools to obtain a better understanding of opioid peptide-receptor interactions. The proposed research uses a combination of chemical, pharmacological and computational techniques, with the rationale that the information obtained from these complimentary methodologies will limit the number of possibilities for interactions of the peptides with receptor residues, greatly facilitating the development of models for the peptides bound to opioid receptors. Continuation of the Independent Scientist Award will allow Dr. Aldrich to expand her expertise in several areas related to her research on opioid peptides. These areas include synthesis (including stereoselective synthesis) of novel amino acid analogs for incorporation into opioid peptide analogs, gaining familiarity with molecular biological techniques to study opioid receptors, and obtaining additional experience with protein characterization by mass spectrometry. Experience in these areas will be synergistic with Dr. Aldrich's expertise in peptide chemistry and significantly enhance her contributions to research in the area of drug abuse.