title: Chemical Platform for the Preparation of Synthetic Orally Active Peptidomimetics with Hemoregulating Activity.
abstract: 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.
authors.affiliation: Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow, 117997, Russia. vdeigin@gmail.com.
authors.forename: Vladislav
authors.identifier: 0000-0003-1257-8697
authors.initials: V
authors.lastname: Deigin
authors.affiliation: Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Olga
authors.initials: O
authors.lastname: Ksenofontova
authors.affiliation: Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Khrushchev
authors.affiliation: Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Oleg
authors.initials: O
authors.lastname: Yatskin
authors.affiliation: Tsyb Medical Radiological Research Center, Ministry of Health of Russia, 249030, Kaluga region, Obninsk, Russia.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Goryacheva
authors.affiliation: Institute of Bioorganic Chemistry, Russian Academy of Sciences, Miklukho-Maklaya 16/10, Moscow, 117997, Russia.
authors.forename: Vadim
authors.initials: V
authors.lastname: Ivanov
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D054659:Diketopiperazines / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D057786:Peptidomimetics / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D054659:Diketopiperazines; D057786:Peptidomimetics
keywords: hematopoiesis; peptidomimetics; piperazine-2,5-diones; synthetic peptides