The Laboratory of Synthetic Vaccines of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya St., 16/10, Moscow 117997, Russia.
The Research Laboratory of the Development of Drug Delivery Systems, St. Petersburg Research Institute of Phthisiopulmonology, Ligovskii Prospect, 2-4, St. Petersburg 191036, Russia.
Int J Mol Sci. 2023 Aug 31;24(17):13534. doi: 10.3390/ijms241713534.
The oral delivery of peptide pharmaceuticals has long been a fundamental challenge in drug development. A new chemical platform was designed based on branched piperazine-2,5-diones for creating orally available biologically active peptidomimetics. The platform includes a bio-carrier with "built-in" functionally active peptide fragments or bioactive molecules that are covalently attached via linkers. The developed platform allows for a small peptide to be taken with a particular biological activity and to be transformed into an orally stable compound displaying the same activity. Based on this approach, various peptidomimetics exhibiting hemostimulating, hemosuppressing, and adjuvant activity were prepared. In addition, new examples of a rare phenomenon when enantiomeric molecules demonstrate reciprocal biological activity are presented. Finally, the review summarizes the evolutionary approach of the short peptide pharmaceutical development from the immunocompetent organ separation to orally active cyclopeptides and peptidomimetics.
口服递送肽类药物一直是药物开发中的一个基本挑战。我们设计了一种基于支化哌嗪-2,5-二酮的新化学平台，用于构建可口服的具有生物活性的肽模拟物。该平台包含一个生物载体，其中含有“内置”的具有功能活性的肽片段或生物活性分子，它们通过连接子共价连接。开发的平台允许具有特定生物活性的小肽被摄取，并转化为具有相同活性的口服稳定化合物。基于这种方法，我们制备了各种具有止血、抗血作用和佐剂活性的肽模拟物。此外，还呈现了罕见的当对映体分子表现出相互生物活性时的现象的新实例。最后，综述总结了从免疫器官分离到具有口服活性的环肽和肽模拟物的短肽药物开发的进化方法。
