An integrated strategy of Natural-Product-Inspired Combinatorial Chemistry (NPICC) and Computation-Guided Synthesis is used to develop an α-hGMII inhibitor with 106-fold selectivity over α-hLM, withinhibitory effect on hepatocellular carcinoma.

Due to the heterogeneous and isomeric nature of glycans, the development of an advanced separation of distinct glycan isomers is essential for glycan research and application. In this study, we utilized porous graphite carbon (PGC) chromatography for the separation of isomeric oligosaccharides without reduction or chemical derivatization at 190 °C in a custom-built heating oven. Furthermore, the fine structures of glycan isomers could be identified by using ultrahigh temperature PGC liquid chromatography mass spectrometry (UHT-PGC-LCMS). A nonreduced hydrolyzed dextran was applied to verify the performance of UHT-PGC. When the temperature of the PGC column was increased from 25 to 190 °C, the liquid chromatography separation power of the nonreduced dextran ladder significantly increased. The advantage of the UHT-PGC column was its high peak capacity with gradient elution in 10 min at 190 °C, 6700 psi, and a 250 μL/min flow rate for native glycan analysis. Four synthetic Lewis antigen isomers were used to elucidate the separation effectiveness in UHT-PGC. Moreover, mass spectrometry-based sequencing to generate specific diagnostic ions from the four synthetic Lewis antigens was used to predict isomeric glycans based on the relative intensity ratio (RIR) of diagnostic ions. The intensities of the diagnostic ions of synthetic isomers were used to identify each isomer of the fucosylated glycan. The results clearly showed that terminal Lewis A and X residues were in the 3- and 6-arms of N-glycan, respectively.

4-Mercapto-4-methyl-2-pentanone (4MMP), a high-impact aroma compound with the box tree and black currant flavors was first identified in wines and could be released by microbial cysteine-S-conjugate β-lyases from its precursors. In this study, various yeasts and bacteria encoding β-lyases were selected to examine their β-lyase activities. A thiol precursor of 4MMP, cysteine-conjugate of 4MMP (cys-4MMP), was synthesized with a purity of >95% in a relatively environmentally friendly approach, and its chemical structure was confirmed by nuclear magnetic resonance spectroscopy. The β-lyase activities of the crude cell extract from the bacteria and yeast strains for different substrates were examined using a colorimetric method. Shewanella putrefaciens cell extract exhibited the highest β-lyase activity for all tested substrates. Additionally, the optimum pH and temperature for their β-lyase activities were determined. To monitor the conversion efficiency of precursor cys-4MMP to 4MMP, liquid chromatography-mass spectrometry was used. Our data indicate that selected bacteria and yeasts could convert cys-4MMP into 4MMP, and S. putrefaciens exhibited the best conversion yield. This study demonstrated the potential use of microbial cell extracts to produce sulfur-containing aroma compounds such as 4MMP.

We present the first report on complete cluster distributions of cytochrome c (molecular weight of 12.4 kDa) and bovine serum albumin ((BSA), molecular weight of 66.4 kDa) with mass-to-charge ratio (m/z) reaching 350,000 and 1,400,000, respectively, by matrix-assisted laser desorption/ionization (MALDI). Large cluster distributions of the analytes were measured by our homemade frequency-scanned quadrupole ion trap (QIT) mass spectrometer with a charge detector. To our knowledge, we report the highest m/z clusters of these two biomolecules. The quantitative results indicate that large clusters ions of cytochrome c and BSA follow the power law (r² > 0.99) with cluster size distribution, which provides experimental evidence for the laser ablation studies of MALDI.