O-GlcNAc transferase （OGT） is one of essential mammalian enzymes, which catalyze the transfer of N-acetylglucosamine from UDP-N-acetylglucosamine （UDP-GlcNAc） to hydroxyl groups of serines and threonines （Ser/Thr） in proteins. Dysregulations of cellular O-GlcNAc have been implicated in diabetes, neurodegenerative disease, and cancer, which brings great interest in developing potent and specific small-molecular OGT inhibitors. In this work, we performed virtual screening on OGT catalytic site to identify potential inhibitors. 7134792 drug-like compounds from ZINC （a free database of commercially available compounds for virtual screening） and 4287550 compounds generated by FOG （fragment optimized growth program） were screened and the top 116 compounds ranked by docking score were analyzed. By comparing the screening results, we found FOG program can generate more compounds with better docking scores than ZINC. The top ZINC compounds ranked by docking score were grouped into two classes, which held the binding positions of UDP and GlcNAc of UDP- GlcNAc. Combined with individual fragments in binding pocket, de novo compounds were designed and proved to have better docking score. The screened and designed compounds may become a starting point for developing new drugs.
We conducted experiments on specially designed microfluidic chips that generate droplets through a microfluidic ow-focusing approach. The fluid flow in the microfluidic channel produced a shear flow field at low Reynolds numbers. The droplets in the microfluidic system exhibited special droplet pattern formations similar to periodic crystal-like lattices because of the competition between shear forces and surface tension. By adjusting the flow rate ratio of the water （droplet phase） to oil （continuous phase） phases and changing the outlet channel widths, the droplets formed monolayer dispersion to double-layer formation to monolayer squeezing when the outlet channel widths were 250 or 300 μm. We also obtained droplets with monolayer dispersion, three-layer arrangements, double-layer squeezing, and monolayer squeezing when the outlet channel width was 350 μm. The outlet channel width was increased to 400 μm, and four-layer arrangements were observed. We also studied the translation of droplet formation, which resulted in a detailed strategy to control drop size and droplet pattern formation for emulsi cation in microfluidic devices. We expect that our strategy can provide theoretical guidance to synthesize dispersion or polydisperse colloid particles.
