CD BioGlyco keeps abreast of scientific developments and keeps updating its Sialylation Inhibitor Development process. Sialyltransferase (ST) can be categorized into four families, including the ST8Sia family. Its function is to promote the linkage to another sialic acid residue in N- or O-glycans, in the α2,8-linkage. Upregulation of ST expression or enhancement of activity will affect the level of cellular sialylation, which ultimately affects a range of physiological and pathological processes. ST8Sia inhibitor development is of great significance to the study of cell communication, immune regulation, tumor invasion, and metastasis. We provide multi-directional ST8Sia inhibitor development services. Based on our advanced Glycosylation Inhibitor Development process, we are confident to do our best.
Fig.1 Different directions of ST8Sia inhibitor development. (CD BioGlyco)
Donor analog inhibitors bind to the active center of the enzyme and occupy the binding site of the natural donor to achieve competitive inhibition. CMP-Sialic acid provides a substrate for ST, which leads to the synthesis of a glycoconjugate containing sialic acid. CMP-Sialic Acid Analogs are potent inhibitors of ST. Currently, researchers have developed CMP-sialic acid analogs with inhibitory activity against ST8Sia. We screen, design, and synthesize CMP-sialic acid analogs and test the strength of their inhibitory activity against ST8Sia. We aim to develop ST8Sia inhibitors with good inhibitory activity and high selectivity.
Cytidine Analogs is also a direction for ST8Sia inhibitor development. Cytidine is an essential group for substrate binding to ST. Donor-based ST inhibitors all retain cytidine. We mainly modify its glycosyl and phosphate portions to develop compounds with high inhibitory activity.
Natural donor substrates bind to the enzyme more strongly than natural acceptor substrates, whereas the selectivity of the enzyme is exclusively related to the acceptor substrate. Researchers began to try to synthesize dual-substrate inhibitors. Based on the donor and acceptor required for sialylation, we screen, design, and synthesize dual-substrate inhibitors containing both donor and acceptor substrates that combine high binding strength and high selectivity.
Technology: Synthesis of donor analogs
Journal: Glycobiology
IF: 4.06
Published: 2008
Results: In this study, two compounds were synthesized: 2'-O-methyl CMP and 5-methyl CMP. 2'-O-Methyl CMP was detected to have a stronger inhibitory effect on ST8Sia-II and ST8Sia-III chemotaxis of ST8Sia-IV, which was comparable to that of CMP. 5-Methyl CMP had a weaker inhibitory effect on the three enzymes. The present study also determined that different modifications of the sugar nucleotide would have different effects on the glycosyltransferase activity.
Fig.2 The structure of CMP, 2'-O-methyl CMP, and 5-methyl CMP. (Miyazaki, et al., 2008)
CD BioGlyco has an advanced glycosylation inhibitor development strategy. We aim to design compounds with high specificity and stability and good inhibitory effect. Please feel free to contact us for more information and a detailed quote on ST8Sia inhibitor development.
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