Chemical Platform for the Preparation of Synthetic Orally Active Peptidomimetics with Hemoregulating Activity
| Autor: | Alexey Khrushchev, Alexandra Goryacheva, Oleg N. Yatskin, Vladislav Deigin, Olga Ksenofontova, Vadim T. Ivanov |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Stereochemistry Peptidomimetic Administration Oral Peptide Bone Marrow Cells Tripeptide Diketopiperazines Biochemistry 03 medical and health sciences chemistry.chemical_compound Mice Structure-Activity Relationship 0302 clinical medicine Drug Discovery Structure–activity relationship Molecule Animals General Pharmacology Toxicology and Pharmaceutics Cell Proliferation Pharmacology chemistry.chemical_classification Dipeptide Dose-Response Relationship Drug Molecular Structure piperazine-2 5-diones Chemistry Communication Organic Chemistry Biological activity Combinatorial chemistry Communications hematopoiesis 030104 developmental biology 030220 oncology & carcinogenesis peptidomimetics Molecular Medicine synthetic peptides Ex vivo Injections Intraperitoneal |
| Zdroj: | Chemmedchem |
| ISSN: | 1860-7187 |
| Popis: | A novel chemical platform based on branched piperazine‐2,5‐dione derivatives (2,5‐diketopiperazines) for creating orally available biologically active peptidomimetics has been developed. The platform includes a diketopiperazine scaffold with “built‐in” functionally active peptide fragments covalently attached via linkers. The concept was applied to two hemostimulatory drugs, the dipeptide thymogen (GluTrp) and the tripeptide stemokin (IleGluTrp). Preparation of a series of respective derivatives is described. Of the five synthesized analogues, three demonstrated high hemostimulatory activity in vivo on intact mice and on ex vivo irradiated bone marrow cells. Prospects of further development of the concept are discussed. |
| Databáze: | OpenAIRE |
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