Sang-Hyun Son

Pre-activation of fully acetylated dodecyl thioglycosides with BSP-Tf2O led to efficient glycosylation at low temperature.

Fully acetylated dodecyl thioglycosides were found to be useful as glycosyl donors by activation with 1-benzenesulfinyl piperidine (BSP) and triflic anhydride (Tf(2)O) at -78 degrees C. The glycosyl acceptor was added to the reaction mixture at the same temperature to furnish various disaccharide, including the protected Lewis a (Le(a)) trisaccharide, in good yields.

Dodecyl thioglycopyranoside sulfates : Novel sugar-based surfactants for enantiomeric separations by micellar electrokinetic capillary chromatography

Four novel chiral anionic surfactants having carbohydrate hydrophilic heads, sodium n‐dodecyl 1‐thio‐β‐D‐glucopyranoside 6‐hydrogen sulfate (6‐βGlcD), sodium n‐dodecyl 1‐thio‐β‐L‐glucopyranoside 6‐hydrogen sulfate (6‐βGlcL), sodium n‐dodecyl 1‐thio‐β‐L‐fucopyranoside 3‐hydrogen sulfate (3‐βFucL), and sodium n‐dodecyl 1‐thio‐α‐L‐rhamnopyranoside 3‐hydrogen sulfate (3‐αRhaL), were synthesized by selective sulfation of the corresponding thioglycosides. Their CMC determined by fluorescence using pyrene as a probe in water was 1.3–2.7 mM. These surfactants found to be useful as chiral selectors for enantiomeric separation by MEKC. The enantiomeric separation was optimized with respect to pH, buffer concentration, and surfactant concentration. Under the optimized conditions (50 mM phosphate buffer at pH 6.5, 30 mM surfactant, 20 kV), the enantiomeric separations of five dansylated amino acids (Dns‐AAs) were achieved within approximately 20 min with the migration order of Val < Met < Leu < Phe < Trp. With 6‐βGlcD, all D‐forms of Dns‐AAs were found to migrate faster than the corresponding L‐forms, whereas the migration order of the enantiomers was completely reversed with the surfactant 6‐βGlcL having inversed absolute configuration of 6‐βGlcD. Among four surfactants examined, β‐anomers were much superior chiral selectors than α‐anomers, and the maximum resolution was obtained with the 6‐deoxy sugar, 3‐βFucL. These results indicated that the structures of the surfactant head groups including their anomeric configurations have significant effects on the enantiomeric separation and the migration behavior in MEKC.

Stereoselective tris-glycosylation to introduce β-(1→3)-branches into gentiotetraose for the concise synthesis of phytoalexin-elicitor heptaglucoside

Dodecyl thioglycosides (3, 4, 5) were prepared by conventional transformation of d-glucose and used as new glycosyl donors for a short-step synthesis of phytoalexin elicitor heptaglucoside. A gentio-tetraoside derivative (6) having three hydroxyl groups was synthesized by NIS-TfOH promoted glycosylate in more than 90% yield followed by selective removal of temporary protective groups. Undesired formation of alpha-glycosides at the introduction of beta-(1-->3)-branches into gentio-oligosaccharides was found to be suppressed by use of a thiophilic reagent system, BSP (1-benzenesulfinyl piperidine)-Tf2O, giving the heptaglucoside in only four glycosylation steps.

Enantiomeric separation by MEKC using dodecyl thioglycoside surfactants: Importance of an equatorially oriented hydroxy group at C-2 position in separation of dansylated amino acids

To investigate the influence of stereogenic centers of sugar‐based surfactants for enantiomeric separation, four n‐dodecyl thioglycoside sulfates (CMC 1.5–3.6 mM) were chosen as micelle‐forming surfactants and five dansylated hydrophobic amino acids were used as test analytes. The analytes were mutually separated by these micelles exhibiting almost similar migration times independent of the used surfactant. Baseline separations of all enantiomers were achieved using both β‐D‐glucose and β‐D‐galactose derivates that have an equatorially oriented hydroxy group at C‐2 position. In contrast, the ability of enantioseparation was markedly decreased in the case of β‐D‐mannose and 2‐deoxy‐β‐D‐glucose derivatives. These results suggested that the structure of C‐2 position of the sugar unit, namely presence of an equatorially oriented hydroxy group, is highly important for the enantiomeric separation of the chosen hydrophobic dansylated amino acids.

Potential-modulated fluorescence spectroscopy of zwitterionic and dicationic membrane-potential-sensitive dyes at the 1,2-dichloroethane/water interface.

AbstractThe previously introduced technique of potential-modulated fluorescence (PMF) spectroscopy was used to study the potential-induced fluorescence change of some different dyes at the polarized 1,2-dichloroethane (DCE)/water (W) interface. A zwitterionic dye (POLARIC 488PPS) showed a PMF response similar to that for the previously studied dye (di-4-ANEPPS) with the same ionic state, and the PMF response was likewise explained by the potential-dependent reorientation of the dye at the DCE/W interface. Though a monocationic dye (POLARIC 488PM) showed no distinct PMF signal, a dicationic dye (di-2-ANEPEQ) showed two relatively weak but detectable PMF signals at lower and higher potential. It has thus been found that the ionic state of a potential-sensitive dye strongly influences the potential-induced reorientation of the dye at the interface and consequently its PMF response. These results support the reorientation/solvatochromic mechanism proposed for “slow” dyes but do not necessarily exclude the electrochromic mechanism proposed for “fast” dyes. PMF spectroscopy would provide useful information on the design of slow dyes for the measurement of the resting potential of cell membranes FigPotential-dependent reorientation of a zwitterionic membrane-potential-sensitive dye (POLARIC 488PPS) at the oil/water interface and its potential-modulated fluorescence signal (inset)

Synthesis and biological evaluation of peptide-derived TSLP inhibitors

Thymic stromal lymphopoietin (TSLP) is a type II cytokine which is associated with most inflammatory allergic disorders in humans. It is produced mainly by epithelial cells with important role in the development of chronic inflammatory diseases by activating T-helper cell type-2 (TH2) pathways. In this study, a total of 16 peptides were prepared by solid phase peptide synthesis based on amino acid sequences of the interface between TSLP and TSLP receptor. Their TSLP inhibition activities were determined by ELISA assay. Among them, three peptides (6-8) exhibited >50% inhibition at concentration of 0.3mM. They can be used as hit compounds for developing peptide-based TSLP inhibitors.

Endoplasmic Reticulum (ER)-Targeted, Galectin-Mediated Retrograde Transport by Using a HaloTag Carrier Protein

Investigations into metabolic processes within the cell have often relied on genetic methods such as forced expression and knockout or knockdown techniques. An alternative approach would be introducing a molecule into the desired location inside the cell. To translocate compounds from outside cells into the endoplasmic reticulum (ER), we constructed a delivery carrier protein. This comprised N‐terminal galectin‐1 for cell‐surface binding (G1), a protease cleavable sequence (ps), a HaloTag domain for attaching exogenous compounds (Halo), and a C‐terminal KDEL sequence for ER retention. Fluorescently labeled G1‐ps‐Halo‐KDEL passed through the Golgi apparatus and reached the ER. By using Man9GlcNAc2‐BODIPY as a cargo compound, the carrier protein was also delivered into the ER with concomitant processing of mannose to Man5,6, by the ER‐resident α1,2‐mannosidase. G1‐ps‐Halo‐KDEL might serve as a new type of delivery carrier protein to direct compounds into the ER.

Synthetic study of 3-fluorinated sialic acid derivatives.

Sialic acid derivatives, analogs, and their conjugates are expected to be pharmaceutical candidates such as anti-influenza drugs and also useful probes for investigating the biological role of glycoconjugates. Derivatives of 3-fluorinated sialic acid (3-F-Sia) have been found to be excellent probes in investigating functions and mechanisms of a series of proteins. Here, we describe the syntheses of 3-F-Sia derivatives, which are useful in making biologically important conjugate probes. A practical method for the construction of 3-fluorinated sialosides based on the stereoselective formation of the corresponding anomeric O-trimethylsilyl ether and their nucleophilic attack by an alkyl halide, an allyl halide in particular, was developed. In addition, details of the synthesis of cytidine monophosphate (CMP)-3-F-Sia bearing a fluorescent tag, which has been proven to show dual functions as a substrate of CMP-sialic acid transporter (CST) and an inhibitor of sialyltransferase (STase), are described.

Recent Advances of Hepsin-Targeted Inhibitors

Hepsin is a type II transmembrane serine protease (TTSP) that plays a crucial role in cell growth and development. Hepsin is highly expressed in prostate cancer (PCa) and associated with its progression and metastasis. Therefore, it has been considered as an attractive biomarker of PCa. Recently, low molecular weight inhibitors targeting hepsin have been developed. Based on the key chemical scaffold, they can be classified into four classes: Indolecarboxamidines, benzamidines, peptide-based analogs, and 2,3-dihydro- 1H-perimidines. In this review, we discuss design strategy, structure-activity relationship (SAR), and binding mode of the four classes of hepsin inhibitors.