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Biocatalyst for Preparation of Glycosides


Promising Biocatalysts for Preparing Natural Medicinal Glycosides

Tech Area / Field

  • CHE-SYN/Basic and Synthetic Chemistry/Chemistry
  • BIO-CHM/Biochemistry/Biotechnology
  • MED-DRG/Drug Discovery/Medicine
  • BIO-IND/Industrial Biotechnology/Biotechnology
  • BIO-DIV/Biodiversity/Biotechnology
  • CHE-ANL/Analytical Chemistry/Chemistry

3 Approved without Funding

Registration date

Leading Institute
State Research Institute of Organic Chemistry and Technology, Russia, Moscow

Supporting institutes

  • All-Russian Research Institute of Medical and Aromatic Herbs, Russia, Moscow


  • Protein Labelling Innovation, The Netherlands, Leiden\nHarvard University / Department of Chemistry and Chemical Biology, USA, MA, Cambridge

Project summary

Cardiotonic glycosides are most prominent among natural glycosides playing an important part in the therapy of cardiovascular diseases.

They are extracted from different herbs, such as as Digitalis, Convallaria majalis, Apocynum cannabinum, Adonis vernalis, Erisymum, Strophantus, etc.

A wide variety of preparations of this class previously proposed and introduced into medical practice gave place to extremely limited list of cardiac glycosides that nowadays find practical application in therapy. With few exceptions, in most cases the therapy lies in the prescription of digoxin (secondary glycoside from Digitalis lanata) orally or intravenously.

The leaves of Digitalis lanata contain specific endogenous enzymes catalyzing the splitting off of the end glucose and the acetyl group from the molecule of primary cardiac glycosides (lanatosides). Cardenolide -161-O-glucohydrolase and lanatoside -151-O-acetylesterase — promising biocatalysts for preparing natural medicinal glycosides of digoxin and digitoxin type — have been extracted from the leaves of Digitalis lanata, purified and partially sequenced.

Provided that the activity of hydrolases in the raw material is high enough, it is convenient to perform the enzymatic degradation of lanatoside C into digoxin with the use of these enzymes. The most objective information can be obtained by NMR spectroscopy and HPLC, which must replace paper chromatography and biological methods of evaluating the activity of cardiotonic medications. To ensure stable activity of glycosidase and esterase during the production it is planned in the framework of this project to develop fundamentally new techniques for isolating the protein concentrate of a certain enzymatic activity which can be added, if necessary, in the course of fermentation for the purpose of controlling the stage of enzymatic hydrolysis of the raw material.

The main goal of this project is to realize modern biotechnological approach to the production and standardization of highly active and demanded in medical practice cardiovascular medications of the series of cardiotonic glycosides, in particular, digoxin.

The project includes five tasks:

Task 1.To explore the growing, picking, drying and storing of Digitalis lanata.
Task 2.To develop a technology of enzymatic hydrolysis of the natural raw material and isolation of digoxin.
Task 3.To determine and improve the methods of control and standardization of primary and secondary glycosides of Digitalis lanata, as well as raw materials and intermediate products.
Task 4. To investigate the enzymatic activity of the raw Digitalis lanata and isolate enzymatic preparations of the standard activity level.
Task 5. To produce experimental batches of digoxin and corglycon, and their pharmaceutical dosage forms.

Practical Project Implementation results in the improvement of techniques of biotechnological production of preparations of digoxin and corglycon, their standardization with the use of advanced physicochemical methods, such as HPLC and NMR spectroscopy, and production of experimental batches which will allow leveling up the quality of domestic medications to European standards.


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