Federalnoe gosudarstvennoe byudzhetnoe uchrezhdenie nauki Institut bioorganicheskoj khimii im. akademikov M.M. Shemyakina i YU.A. Ovchinnikova Rossijskoj akademii nauk (IBKH RAN)
发明人:
Azev Vyacheslav Nikolaevich (RU),Азев Вячеслав Николаевич (RU),Turobov Valerij Igorevich (RU),Туробов Валерий Игоревич (RU),Danilkovich Aleksej Viktorovich (RU),Данилкович Алексей Викторович (RU),Shev
申请号：
RU2017140995
公开号：
RU0002681318C1
申请日:
2017.11.24
申请国别(地区):
RU
年份:
2019
代理人:
摘要：
FIELD: medicine； chemistry.SUBSTANCE: invention relates to the field of medical chemistry, immunology and neurobiology, and is aimed at developing a new agent for the treatment of multiple sclerosis, corresponding to class of biologically active substance – conjugate of immunosuppressive peptide Abu-TGIRIS-Abu with chelating agent – diethylenetriaminopentaacetic acid (DTPA), which is in the form of a coordination complex with the Gd3+ ion. In the framework of the present invention, a method for the preparation of the Gd3+ complex salt with DTPA-Lys-diglycolate-Ahx-Abu-TGIRIS-Abu-NH2 was proposed, where DTPA denotes diethylenetriaminopentaacetic acid, Ahx denotes aminohexanoic acid, Abu denotes α-aminobutyric acid, comprising the following steps: (1) to Abu-TGIRIS-Abu peptide synthesized by the solid-phase method using MBHA-polystyrene as a carrier, without removing it from the polymer substrate, aminohexanoic acid is added to obtain the Ahx-Abu-TGIRIS-Abu-NH2 peptide, connected via residue α-aminobutyric acid to the amino group of MBHA-modified polystyrene, (2) get (S)-9-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)ethyl)-6-(2-(tert-butoxy)-2-oxoethyl)-10-(tert-butoxycarbonyl)-2,2-dimethyl-4,16-dioxo-3,18-dioxa-6,9,15-triazicosan-20-olic acid, (3) to the Ahx-Abu-TGIRIS-Abu peptide attached to the amino group of MBHA-modified polystyrene through the residue α-aminobutyric acid, add the condensing mixture in the form of a solution of (S)-9-(2-(bis(2-(tert-butoxy)-2-oxoethyl)amino)ethyl)-6-(2-(tert-butoxy)-2-oxoethyl)-10-(tert-butoxycarbonyl)-2,2-dimethyl-4,16-dioxo-3,18-dioxa-6,9,15-triazicosan-20-olic acid in dimethylformamide, (4) carry out the removal of the protective groups and the peptide from the substrate, (5) receive the complex salt Gd3+ with DTPA-Lys-diglycolate-Ahx-Abu-TGIRIS-Abu-NH2 by reaction of the modified peptide with the Gd3+ salt. Conjugate can be used as a means of visualizing lymphocytes that are potentially involved in autoimmune damage to the myeli
