Highly sensitive two-dimensional profiling of N-linked glycans by hydrophilic interaction liquid chromatography and dual stacking capillary gel electrophoresis.

Background: N-Glycosylation is one of the most important post-translational modifications in proteins. As the N-glycan profiles in biological samples are diverse and change according to the pathological condition, various profiling methods have been developed, such as liquid chromatography (LC), capillary electrophoresis (CE), and mass spectrometry. However, conventional analytical methods have limitations in sensitivity and/or resolution, hindering the discovery of minor but specific N-glycans that are important both in the basic glycobiology research and in the medical application as biomarkers.

Effects of Synthetic Tetronamides and Methylated Denigrins on Bacterial Quorum Sensing and Biofilm Formation.

Detrimental biofilms of bacterial pathogens cause chronic infections with a high-level tolerance to antibiotics. To identify new control agents, we synthesized and tested a total of 14 tetronamides (including 5 new compounds) and 6 denigrin intermediates on the model species . At a concentration of 50 μg/mL, two tetronamides and two methylated denigrins exhibited significant inhibitory effects against biofilm formation of RP437, e.

Water-Soluble Ionic Metal-Organic Polyhedra as a Versatile Platform for Enzyme Bio-immobilization.

Metal-organic polyhedra (MOPs) can act as elementary structural units for the design of modular porous materials; however, their association with biological systems remains greatly restricted by their typically low stabilities and solubilities in water. Herein, we describe the preparation of novel MOPs bearing either anionic or cationic groups and exhibiting a high affinity for proteins. Simple mixing of the protein bovine serum albumin () and ionic MOP aqueous solutions resulted in the spontaneous formation of MOP-protein assemblies, in a colloidal state or as solid precipitates depending on the initial mixing ratio.

Compositional Analysis and Potent Insecticidal Activity of Supercritical CO Fluid Extracts of L. Leaves.

To mitigate potentially severe food shortages due to the exponential growth of the global population, it is of paramount importance to improve the yield and quality of globally harvested food crops. As pest control contributes to both these aspects, the development of safe and effective pesticides is one of the main strategies pursued in this direction in the context of agricultural chemistry. During our investigation of natural pesticides, a supercritical CO fluid extract of L.

Preparation of Nitrogen Analogues of Ceramide and Studies of Their Aggregation in Sphingomyelin Bilayers.

Ceramides can regulate biological processes probably through the formation of laterally segregated and highly packed ceramide-rich domains in lipid bilayers. In the course of preparation of its analogues, we found that a hydrogen-bond-competent functional group in the C1 position is necessary to form ceramide-rich domains in lipid bilayers [Matsufuji; 2018]. Hence, in the present study, we newly synthesized three ceramide analogues: CerN, CerNH, and CerNHAc, in which the 1-OH group of ceramide is substituted with a nitrogen functionality.

Rhodium(III)-Catalyzed C-H/N-H Alkyne Annulation of Nonsymmetric 2-Aryl (Benz)imidazole Derivatives: Photophysical and Mechanistic Insights.

Rhodium(III) catalysis enabled C-H/N-H alkyne annulation of nonsymmetric imidazole derivatives. This study encompasses the synthesis of imidazoles from a naturally occurring quinoidal compound and their use for the preparation of rigid π-extended imidazole derivatives with outstanding fluorescence. Our study also brings to light the photophysical aspects and the mechanism of the reaction studied via computational calculations.

Bisphenol AF: Halogen bonding effect is a major driving force for the dual ERα-agonist and ERβ-antagonist activities.

17β-Estradiol (E2) is a natural steroid ligand for the structurally and physiologically independent estrogen receptors (ERs) ERα and ERβ. We recently observed that CF-containing bisphenol AF (BPAF) works as an agonist for ERα but as an antagonist for ERβ. Similar results were also observed for the CCl-containing bisphenol designated as HPTE.

1,2- trans Glycosylation via Neighboring Group Participation of 2- O-Alkoxymethyl Groups: Application to One-Pot Oligosaccharide Synthesis.

The use of 2- O-alkoxymethyl groups as effective stereodirecting substituents for the construction of 1,2- trans glycosidic linkages is reported. The observed stereoselectivity arises from the intramolecular formation of a five-membered cyclic architecture between the 2- O-alkoxymethyl substituent and the oxocarbenium ion, which provides the expected facial selectivity. Furthermore, the observed stereocontrol and the extremely high reactivity of 2- O-alkoxymethyl-protected donors allowed development of a one-pot sequential glycosylation strategy that should become a powerful tool for the assembly of oligosaccharides.

Design and synthesis of benzoacridines as estrogenic and anti-estrogenic agents.

Estrogens play undisputedly important physiological roles, but lifetime exposure to estrogens has also been linked to the development of breast cancer. Moreover, imbalanced estrogen levels have been associated with various symptoms such as osteoporosis and menopausal disorders. For the improvement of such estrogen imbalances, estrogenic reagents with regulatory properties have shown promising potential.

Syntheses and Biological Activities of the LMNO, ent-LMNO, and NOPQR(S) Ring Systems of Maitotoxin.

Structure-activity relationship studies of maitotoxin (MTX), a marine natural product produced by an epiphytic dinoflagellate, were conducted using chemically synthesized model compounds corresponding to the partial structures of MTX. Both enantiomers of the LMNO ring system were synthesized via aldol reaction of the LM ring aldehyde and the NO ring ketone. These fragments were derived from a common cis-fused pyranopyran intermediate prepared through a sequence involving Nozaki-Hiyama-Kishi reaction, intramolecular oxa-Michael addition, and Pummerer rearrangement.

Generation of cloned mice and nuclear transfer embryonic stem cell lines from urine-derived cells.

Cloning animals by nuclear transfer provides the opportunity to preserve endangered mammalian species. However, there are risks associated with the collection of donor cells from the body such as accidental injury to or death of the animal. Here, we report the production of cloned mice from urine-derived cells collected noninvasively.

2-Naphthylmethoxymethyl as a Mildly Introducible and Oxidatively Removable Benzyloxymethyl-Type Protecting Group.

2-Naphthylmethoxymethyl (NAPOM) was developed for the protection of various hydroxy (including phenolic hydroxy and carboxy) and mercapto groups. The NAPOM group can be introduced in extremely mild conditions (naphthylmethoxymethyl chloride, 2,6-lutidine, room temperature) without concomitant acyl migration in a 1,2-diol system. Furthermore, selective removal of NAPOM in the presence of naphthylmethyl (NAP) and p-methoxybenzyl (PMB) groups and, conversely, that of PMB in the presence of NAPOM were realized.

Ribosomal synthesis of an amphotericin-B inspired macrocycle.

Here we report in vitro ribosomal synthesis of a natural product-like macrocyclic peptide, inspired by the structure of amphotericin B (AmB), an amphiphilic and membrane-interacting antifungal natural product. This AmB-inspired macrocyclic peptide (AmP), one side of which is composed of hydrophobic terpene, and the other side comprises a peptidic chain, was synthesized utilizing flexizyme-assisted in vitro translation via an unusual but successful initiation with a D-cysteine derivative. The established method for the synthesis of AmPs is applicable to the generation of a diverse AmP library coupled with an in vitro display format, with the potential to lead to the discovery of artificial bioactive amphiphilic macrocycles.

Synthesis and biological activity of the C'D'E'F' ring system of maitotoxin.

Stereoselective synthesis of the C'D'E'F' ring system of maitotoxin was achieved starting from the E' ring through successive formation of the D' and C' rings based on SmI2-mediated reductive cyclization. Construction of the F' ring was accomplished via Suzuki-Miyaura cross-coupling with a side chain fragment and Pd(II)-catalyzed cyclization of an allylic alcohol. The C'D'E'F' ring system inhibited maitotoxin-induced Ca(2+) influx in rat glioma C6 cells with an IC50 value of 59 μM.

Guest responsivity of a two-dimensional coordination polymer incorporating a cholesterol-based co-ligand.

To implement specific guest responsivity, a hydrophobic cholesterol-based co-ligand, cholest-5-en-3-yl-4-isonicotinate (Cholpy), was incorporated into a two-dimensional Hofmann-type Co(II)Ni(II) coordination polymer. The chemically programmed structure successfully demonstrated the unique guest response with remarkable chromatic changes.

Artificial ladder-shaped polyethers that inhibit maitotoxin-induced Ca2+ influx in rat glioma C6 cells.

Maitotoxin (MTX) is a ladder-shaped polyether produced by the epiphytic dinoflagellate Gambierdiscus toxicus. It is known to elicit potent toxicity against mammals and induce influx of Ca(2+) into cells. An artificial ladder-shaped polyether possessing a 6/7/6/6/7/6/6 heptacyclic ring system, which was designed for elucidating interactions with transmembrane proteins, was found to be the most potent inhibitor against MTX-induced Ca(2+) influx that has ever been reported.

A comprehensive overview on genomically directed assembly of aromatic polyketides and macrolide lactones using fungal megasynthases.

Fungal polyketide synthases (PKSs) catalyze a carbon-carbon bond forming reaction in an iterative manner using a variety of acyl-CoA molecules as substrates when biosynthesizing complex polyketides. Although most members from this class of natural products exhibit notable biological activities, often they are naturally produced in trace levels or cultivation of the analyte-producing organism is less than feasible. Appropriately, to contend with the former challenge, one must identify any translational bottleneck and perform functional analysis of the associated enzymes.

Ribosomal synthesis of dehydrobutyrine- and methyllanthionine-containing peptides.

We report here the ribosomal synthesis of methyllanthionine-containing cyclic peptides involving a site-specific incorporation of vinylglycine under the reprogrammed genetic code, followed by the isomerization of the vinylglycine to dehydrobutyrine, and the subsequent intramolecular Michael addition of a cysteine residue placed at a downstream position of the vinylglycine.

Surface plasmon resonance-based detection of ladder-shaped polyethers by inhibition detection method.

Ladder-shaped polyether (LSP) compounds represented by brevetoxins and ciguatoxins were largely discovered in association with seafood poisoning. Thus, a quick quantification method for LSPs is potentially important. We examined a surface plasmon resonance method using desulfated-yessotoxin (dsYTX) immobilized on a sensor chip and phosphodiesterase PDEII in a inhibition detection mode.

Thermal cyclization of nonconjugated aryl-yne-carbodiimide furnishing a dibenzonaphthyridine derivative.

The reagent-free C(2)-C(7) thermal cyclization of a nonconjugated aryl-yne-carbodiimide yielded a dibenzo[b,g][1,8]naphthyridine derivative, whose congeners are known to possess fascinating pharmacological properties. This is the first heteroaromatic compound prepared by the thermal cycloaromatization of "nonconjugated" aryl-ynes.

Interaction of ladder-shaped polyethers with transmembrane alpha-helix of glycophorin A as evidenced by saturation transfer difference NMR and surface plasmon resonance.

Ladder-shaped polyether (LSP) compounds are thought to interact with transmembrane alpha-helices, but direct evidence has scarcely obtained for these interactions. We adopted a transmembrane alpha-helix of glycophorin A, and quantitatively evaluated its interaction with LSPs such as yessotoxin (YTX), desulfated YTX and artificial LSPs, using surface plasmon resonance and saturation transfer difference NMR. As a result, dissociation constants (K(D)) of YTX and desulfated YTX to a transmembrane domain peptide of glycophorin A were determined to be in the submillimolar range.

Convergent synthesis and biological activity of the WXYZA'B'C' ring system of maitotoxin.

The WXYZA'B'C' ring system ( 1) of maitotoxin (MTX) was synthesized in a convergent manner via successive coupling of the W, Z, and C' ring fragments through construction of the XY and A'B' ring systems. The synthetic segment 1 blocked the hemolytic activity elicited by MTX.

Design and synthesis of ladder-shaped tetracyclic, heptacyclic, and decacyclic ethers and evaluation of the interaction with transmembrane proteins.

Ladder-shaped polyether (LSP) toxins represented by brevetoxins and ciguatoxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, we have synthesized artificial ladder-shaped polyethers (ALPs) containing 6/7/6/6 tetracyclic, 6/7/6/6/7/6/6 heptacyclic, and 6/7/6/6/7/6/6/7/6/6 decacyclic systems, based on the convergent method via alpha-cyano ethers. The ALPs possessing the simple iterative structure with different numbers of rings would be useful for structure-activity relationship studies on the molecular length, which is supposed to be important when naturally occurring LSPs elicit their toxicity.

Synthesis and DNA cleaving activity of water-soluble non-conjugated thienyl tetraynes.

Water-soluble non-conjugated thienyl tetraynes (3-6) were synthesized and their DNA cleaving activity was evaluated using electrophoresis, atomic force microscopy (AFM) and Escherichia coli (E. coli) transformation techniques. The amino-functionalized compound 4 was shown to possess an activity to cleave plasmid DNA by both electrophoresis and E.