Innovative approaches to oligoheterocyclic peptidomimetics

描述(申请人提供)：新型多肽仿制药和环多肽仿制药已成为具有更高药理活性的治疗剂设计的吸引人的目标。阿片类镇痛剂的治疗潜力和需求引发了大量的科学努力，这导致了一些新的阿片类镇痛剂的开发和阿片类药物药理知识的显著扩展。需要结构不同的配体来帮助研究止痛效果、成瘾和耐受的机制，并可能导致有效的新形式的止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，用于合成新的寡杂环肽类药物。所有建议的化合物将在不同的检测方法中进行内部筛选，以确定u、Delta和kappa阿片受体上的阿片活性。公共卫生相关性：阿片类镇痛剂对缓解剧烈疼痛有显著益处。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行为的基础上，可以开发具有更理想特性的新的阿片类药物和治疗方法。模拟多肽是一种模拟多肽的生物活性的化合物，同时具有提高生物利用度、生物稳定性、生物效率和相对于亲本多肽的天然生物靶标的生物选择性的优点。肽类药物的例子已经作为天然产物被分离出来，作为从新的亚基合成的文库，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，是越来越重要的药物和生物探针。我们提出了设计和合成独特的寡杂环多肽模拟物和环多肽模拟物。所有建议的化合物将在不同的检测方法中进行内部筛选，以确定u、Delta和kappa阿片受体上的阿片活性。

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.