Towards the synthesis of potential inhibitor of α-mannosidase II designed by computational methods

Authors: Mária Spišáková 1    Maroš Bella 1    Miroslav Koóš 1   
1 Center for Glycomics, Institute of Chemistry, Slovak Academy of Sciences, Dúbravská cesta 9, SK-845 38 Bratislava, Slovakia   
Year: 2016
Section: Organic, bioorganic and pharmaceutical chemistry, pharmacology
Abstract No.: 1384
ISBN: 978-80-972360-0-7

α-Mannosidase II (GM-II) belongs to a family of enzymes that takes part in the biosynthesis of complex and hybrid N-glycans. N-Glycans are glycoproteins in which the oligosaccharide moiety is covalently attached to amide group of asparagine residue by N-glycosidic bond. The key functions of the N-glycans in biological processes include growth, differentiation, signal transduction, receptor activation, immune system modulation, protein folding, cellular adhesion and host-pathogen interaction.1 On the other hand, recent studies showed that N-glycans are present in an increased amount in various types of cancer cells and their metastasis.2 Since GM-II plays the important role in N-glycans biosynthesis, the inhibitors of GM-II attract attention as drug candidates for cancer treatment. Based on the structure of two alkaloids, swainsonine3 and mannostatin A4, which inhibit GM-II, the structure of potential GM-II inhibitor 8 was proposed by using computational methods.

This contribution describes preparation of polyhydroxycyclopentene 4 (in eight synthetic steps starting from D-lyxose) representing the key intermediate for synthesis of target compound 8.

Acknowledgement. Financial support of this work by the Slovak Grant Agency (VEGA grant nos. 2/0064/15 and 2/0024/16) and Slovak Research and Development Agency (APVV grant no. APVV-0484-12) is gratefully appreciated. This contribution is the result of the project implementation: Centre of Excellence for Glycomics, ITMS 26240120031, supported by the Research & Development Operational Programme funded by the ERDF.
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