Towards the synthesis of potential inhibitor of α-mannosidase II designed by computational methods
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
|Section:||Organic, bioorganic and pharmaceutical chemistry, pharmacology|
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.
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