Abstract
Sialic acids cap the glycans of cell surface glycoproteins and glycolipids. They are involved in a multitude of biological processes, and aberrant sialic acid expression is associated with several pathologies, such as cancer. Strategies to interfere with the sialic acid biosynthesis can potentially be used for anticancer therapy. One well-known class of sialylation inhibitors is peracetylated 3-fluorosialic acids. We synthesized 3-fluorosialic acid derivatives modified at the C-4, C-5, C-8, and C-9 position and tested their inhibitory potency in vitro. Modifications at C-5 lead to increased inhibition, compared to the natural acetamide at this position. These structure–activity relationships could also be applied to improve the efficiency of sialic acid metabolic labeling reagents by modification of the C-5 position. Hence, these results improve our understanding of the structure–activity relationships of sialic acid glycomimetics and their metabolic processing.
Highlights
Sialic acids are nine-carbon sugars abundantly expressed at the termini of mammalian glycans on membrane-bound and secreted glycoproteins and glycolipids
Mammalian cells can produce sialic acids via a de novo biosynthesis pathway starting from N-acetylmannosamine (ManNAc) in a three-step enzymatic process
CMP-sialic acids are transported into the Golgi apparatus where they are utilized as a sialyl donor by 20 sialyltransferase isoenzymes which install sialic acids via distinct glycosidic linkages (α2-3, α2-6, or α2-8) on various glycoconjugates (N/ O-glycans, glycolipids) giving rise to so-called sialoglycans
Summary
Sialic acids are nine-carbon sugars abundantly expressed at the termini of mammalian glycans on membrane-bound and secreted glycoproteins and glycolipids. The sialic acid family contains >80 chemically distinct members that are related to the nonulosonic acids, nine-carbon backbone α-keto sugars that are widely found in nature.. CMP-sialic acids are transported into the Golgi apparatus where they are utilized as a sialyl donor by 20 sialyltransferase isoenzymes which install sialic acids via distinct glycosidic linkages (α2-3, α2-6, or α2-8) on various glycoconjugates (N/ O-glycans, glycolipids) giving rise to so-called sialoglycans. Cell surface sialic acids are important modulators of a myriad of biological processes such as the binding and transport of ions, enhancing the viscosity of mucins, regulating glycoprotein halflife, and interacting with sialic acid binding proteins.. Sialic acids play an important role in modulating immune activity.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
