Innovative approaches to oligoheterocyclic peptidomimetics

描述（由申请人提供）：新型的肽类模拟物和环肽类模拟物已经成为设计具有增加药理活性的治疗剂的有吸引力的目标。阿片类镇痛药的治疗潜力和需求已经启动了大量的科学努力，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著扩展。结构多样的配体有助于研究镇痛疗效、成瘾性和耐受性的机制，并可能导致有效的新型镇痛药或药物滥用的替代治疗。因此，我们提出了一种创新的设计来合成新的寡杂环肽模拟物。所有提出的化合物将在不同的测定中筛选mu， delta和kappa阿片受体的阿片活性。公共卫生相关性：阿片类镇痛药为缓解严重疼痛提供了显著的益处。基于对阿片配体-受体相互作用的准确认识和对阿片受体及其相关蛋白的药理行为的清晰认识，可以开发出具有更理想性能的阿片药物和治疗方法。肽模拟物是一种模拟多肽生物活性的化合物，同时具有提高生物利用度、生物稳定性、生物效率和生物选择性等优点，可以对抗母肽的天然生物靶点。模拟肽的例子已经作为天然产物被分离出来，从新的亚基合成为文库，旨在提高受体的亲和力和选择性。它们提供了具有挑战性的合成靶点，并日益成为重要的药物和生物探针。我们提出设计和合成独特的寡杂环类肽和环状类肽。所有提出的化合物将在不同的测定中筛选mu， delta和kappa阿片受体的阿片活性。

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.