Cyclodextrin-based supramolecular nanogels decorated with mannose for short peptide encapsulation.

Nanogels are aqueous dispersions of hydrogel particles formed by physically or chemically cross-linked polymer networks of nanoscale size. Herein, we devised a straightforward technique to fabricate a novel class of physically cross-linked nanogels via a self-assembly process in water involving α-cyclodextrin and a mannose molecule that was hydrophobically modified using an alkyl chain. The alkyl chain-modified mannose was synthesized in five steps, starting with D-mannose.

"Click" Chemistry for the Functionalization of Graphene Oxide with Phosphorus Dendrons: Synthesis, Characterization and Preliminary Biological Properties.

Two families of phosphorhydrazone dendrons having either an azide or an alkyne linked to the core and diverse types of pyridine derivatives as terminal functions have been synthesized and characterized. These dendrons were grafted via click reaction to graphene oxide (GO) functionalized with either alkyne or azide functions, respectively. The resulting modified-GO and GO-dendrons materials have been characterized by Fourier Transform Infrared (FTIR), Raman spectroscopy (RS), and Magic Angle Spinning Nuclear Magnetic Resonance (MAS NMR) analyses.

Phenothiazine- and Carbazole-Cyanochalcones as Dual Inhibitors of Tubulin Polymerization and Human Farnesyltransferase.

In the search for innovative approaches to cancer chemotherapy, a chemical library of 49 cyanochalcones, , , and , was designed as dual inhibitors of human farnesyltransferase (FTIs) and tubulin polymerization (MTIs) (FTIs/MTIs), two important biological targets in oncology. This approach is innovative since the same molecule would be able to interfere with two different mitotic events of the cancer cells and prevent these cells from developing an emergency route and becoming resistant to anticancer agents. Compounds were synthesized by the Claisen-Schmidt condensation of aldehydes with -3-oxo-propanenitriles under classical magnetic stirring and under sonication.

An Optimized Workflow for the Discovery of New Antimicrobial Compounds Targeting Bacterial RNA Polymerase Complex Formation.

Bacterial resistance represents a major health problem worldwide and there is an urgent need to develop first-in-class compounds directed against new therapeutic targets. We previously developed a drug-discovery platform to identify new antimicrobials able to disrupt the protein-protein interaction between the β' subunit and the σ initiation factor of bacterial RNA polymerase, which is essential for transcription. As a follow-up to such work, we have improved the discovery strategy to make it less time-consuming and more cost-effective.

Biogenesis of a Bacteriophage Long Non-Contractile Tail.

Siphoviruses are main killers of bacteria. They use a long non-contractile tail to recognize the host cell and to deliver the genome from the viral capsid to the bacterial cytoplasm. Here, we define the molecular organization of the Bacillus subtilis bacteriophage SPP1 ~ 6.

Elastase inhibitory activity of secondary metabolites from the fungus CF-231658.

Three known compounds were isolated from CF-231658; 2,7-dihydroxy naphthalene (), virgaricin B () and virgaricin (). The isolated compounds was obtained from liquid-state and agar-supported fermentation using Amberlite XAD-16 solid-phase extraction during the cultivation step. Their structures were elucidated on the basis of 1D and 2D NMR as well as HRMS spectroscopic analyses.

Dihydrouridine synthesis in tRNAs is under reductive evolution in Mollicutes.

Dihydrouridine (D) is a tRNA-modified base conserved throughout all kingdoms of life and assuming an important structural role. The conserved dihydrouridine synthases (Dus) carries out D-synthesis. DusA, DusB and DusC are bacterial members, and their substrate specificity has been determined in .

Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity.

Our previous study found that desmethylxanthohumol () inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol () and its dimer analogue rottlerone () exhibited more potent α-glucosidase inhibitory activity than . The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity.

Indolizine-phenothiazine hybrids as the first dual inhibitors of tubulin polymerization and farnesyltransferase with synergistic antitumor activity.

In the incessant search for innovative cancer control strategies, this study was devoted to the design, synthesis and pharmacological evaluation of dual inhibitors of farnesyltransferase and tubulin polymerization (FTI/MTIs). A series of indolizine-phenothiazine hybrids 16 (amides) and 17 (ketones) has been obtained in a 4-step procedure. The combination of the two heterocycles provided potent tubulin polymerization inhibitors with similar efficiency as the reference phenstatin and (-)-desoxypodophyllotoxin.

Purification, Toxicity and Functional Characterization of a New Proteinaceous Mussel Biotoxin from Bizerte Lagoon.

The marine environment is known to be occupied by microorganisms. The potential toxicity of some of these marine microorganisms, that are capable of producing unknown biotoxins, has always been underestimated. Indeed, these biotoxins may be a threat to human health through the consumption of contaminated seafood and fish.

Synthesis of tetracyclic oxindoles and evaluation of their α-glucosidase inhibitory and glucose consumption-promoting activity.

A series of tetracyclic oxindole derivatives was synthesized by asymmetric 1, 3-dipole reaction in 2-4 steps in 57-86% overall yields. These compounds were evaluated for α-glucosidase inhibitory and glucose consumption-promoting activity in vitro. Compound 4l competitively and reversibly inhibited α-glucosidase (IC = 3.

Isolation and structural identification of a new T1-conotoxin with unique disulfide connectivities derived from .

Background: Conopeptides are neuropharmacological peptides derived from the venomous salivary glands of cone snails. Among 29 superfamilies based on conserved signal sequences, T-superfamily conotoxins, which belong to the smallest group, include four different frameworks that contain four cysteines denominated I, V, X and XVI. In this work, the primary structure and the cysteine connectivity of novel conotoxin of were determined by tandem mass spectrometry using collision-induced dissociation.

Enhanced antitumor potential induced by chloroacetate-loaded benzophenones acting as fused tubulin-pyruvate dehydrogenase kinase 1 (PDHK1) ligands.

The majority of cancers detected every year are treated with anti-cancer compounds. Unfortunately, many tumors become resistant to antineoplastic drugs. One option is to use cocktails of compounds acting on different targets to try to overcome the resistant cells.

tRNA 2'-O-methylation by a duo of TRM7/FTSJ1 proteins modulates small RNA silencing in Drosophila.

2'-O-Methylation (Nm) represents one of the most common RNA modifications. Nm affects RNA structure and function with crucial roles in various RNA-mediated processes ranging from RNA silencing, translation, self versus non-self recognition to viral defense mechanisms. Here, we identify two Nm methyltransferases (Nm-MTases) in Drosophila melanogaster (CG7009 and CG5220) as functional orthologs of yeast TRM7 and human FTSJ1.

Combining 3D single molecule localization strategies for reproducible bioimaging.

Here, we present a 3D localization-based super-resolution technique providing a slowly varying localization precision over a 1 μm range with precisions down to 15 nm. The axial localization is performed through a combination of point spread function (PSF) shaping and supercritical angle fluorescence (SAF), which yields absolute axial information. Using a dual-view scheme, the axial detection is decoupled from the lateral detection and optimized independently to provide a weakly anisotropic 3D resolution over the imaging range.

Exploring isoxazoles and pyrrolidinones decorated with the 4,6-dimethoxy-1,3,5-triazine unit as human farnesyltransferase inhibitors.

Unprecedented triazinyl-isoxazoles were afforded via an effective cycloaddition reaction between nitrile oxides and the scarcely described 2-ethynyl-4,6-dimethoxy-1,3,5-triazine as dipolarophile. The biological evaluation of the newly synthesized compounds showed that the inhibition of human farnesyltransferase by zinc complexation could be improved with triazine-isoxazole moieties. The replacement of the isoxazole unit by a pyrrolidin-2-one was detrimental to the inhibitory activity while the pyrrolidin-2-thione derivatives conserved the biological potential.

Molecular basis for transfer RNA recognition by the double-stranded RNA-binding domain of human dihydrouridine synthase 2.

Double stranded RNA-binding domain (dsRBD) is a ubiquitous domain specialized in the recognition of double-stranded RNAs (dsRNAs). Present in many proteins and enzymes involved in various functional roles of RNA metabolism, including RNA splicing, editing, and transport, dsRBD generally binds to RNAs that lack complex structures. However, this belief has recently been challenged by the discovery of a dsRBD serving as a major tRNA binding module for human dihydrouridine synthase 2 (hDus2), a flavoenzyme that catalyzes synthesis of dihydrouridine within the complex elbow structure of tRNA.

Hierarchical supramolecular platelets from hydrophobically-modified polysaccharides and α-cyclodextrin: Effect of hydrophobization and α-cyclodextrin concentration on platelet formation.

Micro- and nano-platelets are a group of particles with typical flat surfaces and hexagonal shape. They are obtained by hierarchical self-assembly in water of α-cyclodextrin and polysaccharides hydrophobically-modified with alkyl chains. It is expected that the formation of well structured and cohesive platelets is driven by the interaction between alkyl chains grafted on polysaccharides and α-cyclodextrin.

Quantitative Tandem Affinity Purification, an Effective Tool to Investigate Protein Complex Composition in Plant Hormone Signaling: Strigolactones in the Spotlight.

Phytohormones tightly regulate plant growth by integrating changing environmental and developmental cues. Although the key players have been identified in many plant hormonal pathways, the molecular mechanisms and mode of action of perception and signaling remain incompletely resolved. Characterization of protein partners of known signaling components provides insight into the formed protein complexes, but, unless quantification is involved, does not deliver much, if any, information about the dynamics of the induced or disrupted protein complexes.

Synthesis & α-glucosidase inhibitory & glucose consumption-promoting activities of flavonoid-coumarin hybrids.

Aim: The research of novel and potent antidiabetic agents is urgently needed for the control of the exploding diabetic population. We previously reported the synthesis and antidiabetic activity of natural 8-(6"-umbelliferyl)-apigenin (1), but its antidiabetic targets are not known. Therefore, four series of derivatives were synthesized and evaluated for their antidiabetic activities.

Unveiling structural and functional divergences of bacterial tRNA dihydrouridine synthases: perspectives on the evolution scenario.

Post-transcriptional base modifications are important to the maturation process of transfer RNAs (tRNAs). Certain modifications are abundant and present at several positions in tRNA as for example the dihydrouridine, a modified base found in the three domains of life. Even though the function of dihydrourine is not well understood, its high content in tRNAs from psychrophilic bacteria or cancer cells obviously emphasizes a central role in cell adaptation.

Study of the Construction of the Tiacumicin B Aglycone.

Our study of the synthesis of the aglycone of tiacumicin B is discussed here. We imagined two possible strategies featuring a main retrosynthetic disconnection between C13 and C14. The first strategy was based on Suzuki-Miyaura cross-coupling of 1,1-dichloro-1-alkenes, but the failure of this pathway led us to use a Pd/Cu-dual-catalyzed cross-coupling of alkynes with allenes that had never been implemented before in a total synthesis context.

First investigations for the characterization of glucosamine-6-phosphate synthase by capillary electrophoresis.

The enzyme glucosamine-6-phosphate synthase (GlmS) is an important point of metabolic control in biosynthesis of amino sugar-containing macromolecules and is therefore a potential target in order to design antibacterial and antifungal drugs. It has two oligomerization states, which are the active dimer and the inactive hexamer. For the first time, the potential of CE to separate and quantify the two forms was studied.