CD BioGlyco is committed to providing high-quality Glycosylation Inhibitor Development services. O-GlcNAc glycosylation modification is a type of post-translational modification prevalent in prokaryotes and eukaryotes. Throughout the process, OGA is responsible for hydrolyzing GlcNAc off the protein. It is a hexosaminidase present in the cytoplasm and nucleus. O-GlcNAc glycosylation modification associates and participates in the regulation of a variety of cellular processes, including transcription and translation, nutrient and stress perception, neuronal function, cell cycle, etc. The development of O-GlcNAc-based inhibitors is necessary. We provide a one-shop OGA inhibitor development services.
Fig.1 OGA inhibitor development service. (CD BioGlyco)
Most of the OGA inhibitors developed today are competitive inhibitors, being analogs of GlcNAc or reaction intermediates. They bind the active center of the enzyme competitively with the substrate. Based on the types of OGA inhibitors reported, we screen, design, and synthesize compounds that inhibit OGA.
The N-phenyl carbamate portion of PUGNAc captures more binding energy, allowing it to better embed itself in the enzyme pocket and thus inhibit OGA enzyme activity. We design and synthesize PUGNAc derivatives and test their inhibitory effects.
NAG-thiazoline is a transition state analog of OGA hydrolysis and better inhibits human OGA. We design and synthesize NAG-thiazoline derivatives and test their inhibitory effect.
We synthesize compound libraries using the chick-chemistry approach. This is followed by a high-throughput screening for enzyme activity, which leads to the identification of compounds that effectively inhibit OGA enzyme activity. Finally, we conduct a series of cytological experiments on the compounds. In addition, we use computer-aided design and synthesis of potentially active analogs by studying the crystal structure of the OGA homologous enzyme. The focus of our development is on reducing Ki and improving inhibition and specificity.
Journal: Bioorganic Chemistry
Results: In this study, diaminocyclopentanes were modified differently and their inhibitory effect on OGA was investigated. A series of novel derivatives based on the diaminocyclopentane core structure were developed. These compounds were found to inhibit the enzymatic activity of OGA. These compounds are selective and reversible non-transition state inhibitors of OGA and can mimic an "extended substrate".
Fig.2 Process of OGA inhibitor development. (Weber, et al., 2023)
CD BioGlyco has been supporting research in the field of glycobiology through a series of high-quality products and related services. Our experienced scientists and technicians will do their best to provide you with the best inhibitor development services. Please feel free to contact us to inquire about the development direction and details of OGA inhibitor development. We look forward to hearing from you. We will be happy to serve you.