CD BioGlyco aims to contribute to research in the field of glycobiology through efficient Glycosylation Inhibitor Development services. Sialylation is present in many organisms. It is a glycosylated modification process catalyzed by one or more sialyltransferase (ST) and sialidase applying a common sialic acid donor to synthesize. Sialylation is integral to cellular function and mediates many important physiological and pathological processes. The development of inhibitors of sialylation is critical to the study of these physiological and pathological processes. To meet the needs of our clients for different aspects of research and to advance the development of glycobiology, we offer multidirectional sialylation inhibitor development services.
Fig.1 Sialylation inhibitor development. (CD BioGlyco)
Based on the currently developed class of inhibitors, we develop sialylation inhibitors from the following two aspects.
Up-regulation or enhancement of ST expression affects the level of cellular sialylation, which ultimately influences a wide range of physiological and pathological processes. For this reason, we offer services for the development of ST inhibitors. ST inhibitor acts by directly binding to the active site of the ST enzyme, thereby interfering with its enzymatic activity. This inhibition prevents the transfer of sialic acid residues to the glycoconjugate, leading to a reduction in sialylation levels. ST is categorized into four families based on the different positions of attaching the sialic acid residues to the sugar chains: the ST3Gal family (including types I-VI), the ST6Gal (including types I-II), the ST8Sia family (including types I-VI), and the ST6GaINAc family (including types I-VI). We use different drug design strategies for different ST subtypes, including the following:
Synthesizing the types of inhibitors that have been developed so far, we screen, design, and synthesize sialylation inhibitors from the following aspects.
Fig.2 Types of inhibitors developed. (CD BioGlyco)
Many natural derivatives are reported as potential ST inhibitors, such as lithocholic acid derivatives and flavonoid derivatives. Some of these compounds are found to inhibit ST and ultimately affect the sialylation process.
We design inhibitors corresponding to the receptor types of different ST subtypes. We will modify the receptors and test the strength of their inhibitory activity.
CMP-Neu5Ac is a natural donor of sialic acid. It is a donor substrate for various STs. Regardless of their origin and receptor specificity, donor-analog ST inhibitors exert inhibitory activity by competing with the natural glycosyl donor to occupy the donor-enzyme binding site. We rationally design and optimize the mimicry of natural donor inhibitors by modification of nucleoside and sialic acid parts, etc.
The modification of the nucleoside part is the modification and substitution of cytidine residues. The modification of the sialic acid portion is considered to be one of the most effective sialylation inhibitor development strategies to date. We design, synthesize, and test the inhibitory effect of different derivatives, such as cyclic derivatives, phenyl derivatives, etc. Cytidine is an essential group for substrate and enzyme binding, whereas free sialic acid has no inhibitory activity. Most donor analog ST inhibitors retain the cytidine fraction. Therefore we modify mainly the sialic acid part and the phosphate part.
Based on these several inhibitor development strategies, to provide more detailed sialylation inhibitor development services to our clients, we refine our services into the following parts:
Our sialylation inhibitor development services include, but are not limited to, the above. Based on the use of a variety of inhibitor development tools (e.g., high-throughput screening (HTS), computer-assisted drug design, etc.), our inhibitor development efficiency is greatly improved.
Technology: Molecular docking simulation
Journal: Journal of Medicinal Chemistry
Results: In this study, an attempt was made to incorporate an amide bond at the C-2 position of the CMP-Neu5Ac transition state analog. Simple aromatic or aliphatic rings were also used instead of sialic acid. All the synthesized compounds were tested and showed better α(2-6)-sialyltransferase inhibitory activity. Their binding ability to the enzyme was stronger than that of CMP-Neu5Ac. The present study suggests that amide is a key element in the mimicry of transition-state substances.
Fig.3 Designed transition-state analogues with amide bonds. (Guo, et al., 2017)
At CD BioGlyco, our goal has always been to provide quality and quantity-assured glycosylation inhibitor development services. To this end, we are constantly improving our inhibitor development process. Welcome to contact us for more information and quotation on sialylation inhibitor development. Our experienced team and good project management system will provide you with the best quality inhibitor development services.