Innovative approaches to oligoheterocyclic peptidomimetics

寡杂环肽模拟物的创新方法

• 批准号: 7738782
• 负责人: Adel Nefzi
• 金额: $ 22.5万
• 依托单位: TORREY PINES INST FOR MOLECULAR STUDIES
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7738782
• 关键词: Innovative; approaches; oligoheterocyclic; peptidomimetics

DESCRIPTION (provided by applicant): Novel class of peptidomimetics, and cyclic peptidomimetics have become appealing targets for the design of therapeutic agents with increased pharmacological activities. Therapeutic potential and demand of opioid analgesics have initiated numerous amounts of scientific efforts, which have resulted in development of a number of new opioid analgesics and significant expansion of knowledge on the opioid pharmacology. Structurally diverse ligands are needed to aid in the study of the mechanisms of analgesic efficacy, addiction and tolerance, and may lead to effective new forms of analgesics or alternative treatments for drug abuse. Therefore, we propose an innovative design for the synthesis of new oligoheterocyclic peptidomimetics. All the proposed compounds will be screened internally in different assays for opioid activity in mu, delta, and kappa opioid receptors. PUBLIC HEALTH RELEVANCE: Opioid analgesics provide outstanding benefits for relief of severe pain. New opioid drugs and therapies with more desirable properties can be developed on the bases of accurate insight of the opioid ligand-receptor interaction and clear knowledge of the pharmacological behavior of opioid receptors and the associated proteins. Peptidomimetics are compounds which mimic the biological activity of peptides while offering the advantages of increased bioavailability, biostability, bioefficiency, and bioselectivity against the natural biological target of the parent peptide. Examples of peptidomimetics have been isolated as natural products, synthesized as libraries from novel subunits, aiming to improve receptor affinity and selectivity. They offer challenging synthetic targets and are increasingly important medicinal agents and biological probes. We propose the design and the synthesis of unique oligoheterocyclic peptidomimetics and cyclic peptidomimetics. All the proposed compounds will be screened internally in different assays for opioid activity in mu, delta, and kappa opioid receptors.

描述（由申请人提供）：新型肽模拟物和环状肽模拟物已成为设计具有增加的药理学活性的治疗剂的有吸引力的靶标。阿片类镇痛药的治疗潜力和需求引发了大量的科学努力，这导致了许多新的阿片类镇痛药的开发和阿片类药理学知识的显着扩展。需要结构多样的配体来帮助研究镇痛功效、成瘾和耐受性的机制，并且可能导致有效的新形式的镇痛剂或药物滥用的替代治疗。因此，我们提出了一种新的寡杂环肽模拟物的合成的创新设计。所有拟定化合物均将在不同试验中进行内部筛选，以确定μ、δ和κ阿片受体中的阿片活性。公共卫生相关性：阿片类镇痛药在缓解重度疼痛方面具有突出的获益。在准确了解阿片配体-受体相互作用和清楚了解阿片受体及其相关蛋白的药理学行为的基础上，可以开发具有更理想性质的新阿片药物和治疗方法。肽模拟物是模拟肽的生物活性同时提供针对母体肽的天然生物靶标的增加的生物利用度、生物稳定性、生物效率和生物选择性的优点的化合物。肽模拟物的实例已作为天然产物分离，作为文库从新亚基合成，旨在改善受体亲和力和选择性。它们提供了具有挑战性的合成靶标，并且是越来越重要的药物和生物探针。我们提出了独特的寡杂环肽模拟物和环状肽模拟物的设计和合成。所有拟定化合物均将在不同试验中进行内部筛选，以确定μ、δ和κ阿片受体中的阿片活性。