Dol-P-Man is the mannose donor for glycosylphosphatidylinositol (GPI) mannosyltransferase reaction, which is an important intermediate product and has important functions within cells. Dol-P-Man is an esterified compound composed of phosphate esters of long-chain fatty alcohols (dolichol) and mannose. In the cytoplasm, glucose-6-phosphate is converted into mannose-6-phosphate through the action of a series of enzymes and then reacts with dolichol to form Dol-P-Man. It is then transferred to the endoplasmic reticulum (ER) chamber through specific transporters, where it serves as a substrate to participate in the protein glycosylation reaction and transfers the sugar group to the target protein. Based on this mechanism, CD BioGlyco provides professional Dol-P-Man inhibitor development services.
CD BioGlyco has established a huge compound database, and we use efficient high-throughput screening (HTS) and computer-assisted technology to screen potential Dol-P-Man inhibitors.
CD BioGlyco conducts structure-activity relationship research on the initially screened Dol-P-Man inhibitors and provides chemical synthesis and structure optimization services based on the research results to improve their physical and chemical properties. At the same time, we provide purification and analysis for synthesized Dol-P-Man inhibitors.
CD BioGlyco establishes a suitable experimental system to evaluate the inhibitory activity of Dol-P-Man against the enzyme. We purify or express a variety of Dol-P-Man enzymes, react the screened inhibitors with Dol-P-Man enzymes, and measure parameters such as their affinity to the enzyme, rate constant, and inhibition mechanism through appropriate detection methods to determine the best Dol-P-Man inhibitors. For example, 2-deoxy-2-amino-mannose inhibits α-1,2 mannosyltransferase, and a glucose analog (2-deoxy-2-fluoro-D-Glc) competitively binds to Dol-P-Man synthase, thereby blocking the normal synthesis process of Dol-P-Man.
CD BioGlyco also provides activity verification for Dol-P-Man inhibitors at the cellular level and in overall biological systems. We use cell and animal models to evaluate the biological activity, toxicity, and efficacy of Dol-P-Man inhibitors to determine their potential in disease treatment.
Fig.1 Dol-P-Man inhibitor development service. (CD BioGlyco)
Technology: Thin-layer chromatography
Journal: Journal of Biological Chemistry
Results: The authors studied the effect of mannosamine (ManN) on the synthesis of GPI anchor precursors in mammalian cells. ManN inhibited the biosynthesis of Man3GPIs, whose structure was represented as H6, H7, and H8 from HeLa cells. HeLa cells were treated with different concentrations of ManN and labeled with [3H]Man. The results showed that a dose-dependent inhibition of the synthesis of Man3GPIs was detected. The authors believed that the peak between 14.5 and 15.2cm in the figure was Dol-P-Man, and the relative amount of the peak increased with increasing ManN concentration. Research showed that the inhibitory mechanism of ManN was the inhibition of α-1,2-mannosyltransferase.
Fig.2 Effect of ManN on GPI-anchored precursor synthesis in HeLa cells. (Sevlever & Rosenberry, 1993)
CD BioGlyco utilizes diverse chemical libraries for HTS to discover superior compounds against Dol-P-Man. We will provide custom services based on client needs and flexibly respond to project requirements to achieve the best Dol-P-Man inhibitor development results. Please feel free to contact us for specific details if you require quality inhibitor development service.