Group of modified nucleosides synthesis

Laboratory of biotechnology

Head: Anatoliy Miroshnikov, member of the academy of sciences
aiv@ibch.ru

One of the main areas of work is a development of the fundamental and applied aspects of biotechnology for the production of drugs, based on modified nucleoside, for subsequent deployment into biopharmaceuticals production. The other area is a development of biocatalytic technologies of new modified nucleosides for the study of their antiviral and antitumor activities.

 

Partners:

  • Postovsky Institute of Organic Synthesis Ural Branch of the Russian Academy of Sciences FASO Russia – Synthesis of new benzoimidazole bases.
  • Lomonosov Institute of Fine Chemical Technologies, Moscow Technical University, Laboratory of Biotechnology - Synthesis of new 1,2,4-triazole bases.
  • Institute of Bioorganic Chemistry of National Academy of Sciences, Belarus - Collaboration in field of cascade technologies for synthesis of modified nucleosides.
  • Engelgardt Institute of Molecular Biology - Synthesis of feximeric heterocyclic bases for obtaining of new nucleosides.
  • Institute of Experimental Diagnostics and Therapy of Tumors RONC - investigation of cytotoxicity of series of new modified nucleosides.
  • Ivanovsky Institute of Virology - Testing of antivirus activity of new nucleosides in vitro and in vivo.

Patents:

  • Konstantinova I.D., Esipov R.S., Muravieva T.I., et all. A method of producing 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (ribavirin). Patent RU № 2230118, 10.07.2004.
  • Berzin V.B., Dorofeeva Е.V., Leonov V.N., et all. A method of producing 2,6-dichloro-9-(2',3',5'-tri-О-acetyl-β-D–ribofuranosyl)purine. Patent RU № 2324699, 05.02.2008.
  • Berzin V.B., Dorofeeva Е.V., Leonov V.N., et all. A method of producing 2-chloroadenosine. Patent RU № 2324698, 05.02.2008.
  • Berzin V.B., Dorofeeva Е.V., Leonov V.N., Miroshnikov А.I. A method of producing 2-amino-6-azido-9-(2',3',5'-tri-О-acetyl-β-D–ribofuranosyl)purine. Patent RU № 2326124, 05.02.2008.
  • Berzin V.B., Dorofeeva Е.V., Leonov V.N., et all. A method of producing 2',3',5'-tri-О-acetyl-2-fluoroadenosine. Patent RU № 2325395, 05.02.2008.
  • Konstantinova I.D., Antonov К.V., Berzin V.B., et all. A method of producing 9-(β-D-arabinofuranosyl)-2-fluoroadenosine. Patent RU № 2368662, 27.09.2009.
  • Konstantinova I.D., Fateev I.V., Miroshnikov А.I. A method of producing 1-beta-D-ribofuranosyl-1,2,4-triazol-3-carboxamide. Patent RU № 2480218, 27.04.2013.
  • Konstantinova I.D., Eletskaya B.Z., Dorofeeva Е.V., et all. A method of producing 9-beta-D-arabinofuranosyl-6-(Nα-L-serylamido)-2-chloropurine. Patent RU № 2563257, 21.08.2015.
  • Konstantinova I.D., Fateev I.V., Miroshnikov А.I. A method of producing purine nucleosides series of β-D-арабинофуранозы». Patent application RU № 201514771, 06.11.2015, decision from 30.03.2017.

1. The biotechnology laboratory has developed and tested technologies for the synthesis of drugs used in modern clinical practice for the treatment of oncohematological diseases:

  • Cladribine is used for as a first and second-line treatment for symptomatic hairy cell leukemia and for B-cell chronic lymphocytic leukemia and is administered by intravenous infusion; Cladribine Tablets (CLARITY) are used for a treatment of multiple sclerosis for patients with relapsing–remitting form of disease.
  • Fludara - B-cell chronic lymphocytic leukemia, non-Hodgkin's lymphoma low grade and follicular B-cell lymphoma and lymphoma cells from the mantle zone (tablet form).
  • Nelarabine - T-cell acute lymphoblastic leukemia and T-cell lymphoblastic lymphoma (in patients with refractory to chemotherapy or recurrent disease).
  • Clofarabine - treatment of acute lymphoblastic leukemia in children older than 1 year with relapse or refractory to therapy after application, at least two previous chemotherapy regimens and in the absence of other ways of achieving sustained remission.

The technologies have been scaled and tested in terms of the pharmaceutical production companies of OAO "Pharmsynthez" (St-Petersburg) and Zao "R-Pharm" (Moscow). The deployment of those technologies on those enterprises is constrained by the need to conduct clinical studies of the substances obtained and the small demand for the RF market (0.5 to 2 kg).

2. Metabolically resistant analogues of the nucleoside antibiotic cordycepin are obtained. Those substances are of great interest for the therapy of African human trypanosomiasis (HAT).

3. Biotechnological approaches to synthesis of pharmaceutical substances of antiviral drugs - ribavirin, vidarabine, didanosine - have been developed.

NamePositionContacts
Irina Konstantinova, Ph.D.s. r. f.kid1968@yandex.ru+7(495)330-72-47#102
Aleksej Kayushin, Ph.D.s. r. f.kaushin@ibch.ru+7(495)3366833
Vladimir Leonov, Ph.D.s. r. f.+7(495)3362922
Elena Dorofeeva, Ph.D.r. f.+7(495)336-29-22
Inessa Muzykar. f.mis_kou@mail.ru+7(916)126-78-63
Ilya Fateev, Ph.D.r. f.ifateev@gmail.com
Maria Kharitonovaj. r. f.
Maria BerzinaPhD stud.berzina_maria@mail.ru
Ol'ga Tikhomirovaeng.obtikh@mail.ru+7(330)336-29-22
Barbara Eletskayseng.fraubarusya@gmail.com
Olga Smirnovaeng.gescheites@gmail.com
A Denisovaeng.
Ol'ga Lutoninares. eng.+7(495)3362922
Konstantin Antonovproc. eng.+7(495)330-72-47#102

Anatoliy Miroshnikov

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. 53, office. 6601
  • Phone: +7(495)330-59-38
  • E-mail: aiv@ibch.ru