Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores.

ABSTRACT: Cyclic N-propargyl α-peptoids of various sizes were prepared by way of macrocyclizations of linear N-substituted oligoglycines. These compounds were used as molecular platforms to synthesize a series of iminosugar clusters with different valency and alkyl spacer lengths by means of Cu(I)-catalysed azide-alkyne cycloadditions. Evaluation of these compounds as α-mannosidase inhibitors led to significant multivalent effects and further demonstrated the decisive influence of scaffold rigidity on binding affinity enhancements.

SUBMITTER: Lepage ML

PROVIDER: S-EPMC4077385 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of the first examples of iminosugar clusters based on cyclopeptoid cores.

Lepage Mathieu L ML Meli Alessandra A Bodlenner Anne A Tarnus Céline C De Riccardis Francesco F Izzo Irene I Compain Philippe P

Beilstein journal of organic chemistry 20140623

Cyclic N-propargyl α-peptoids of various sizes were prepared by way of macrocyclizations of linear N-substituted oligoglycines. These compounds were used as molecular platforms to synthesize a series of iminosugar clusters with different valency and alkyl spacer lengths by means of Cu(I)-catalysed azide-alkyne cycloadditions. Evaluation of these compounds as α-mannosidase inhibitors led to significant multivalent effects and further demonstrated the decisive influence of scaffold rigidity on bin ...[more]

PMID: 24991295

Similar Datasets

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores.

Project description:The synthesis and photophysical properties of the first examples of iminosugar clusters based on a BODIPY or a pyrene core are reported. The tri- and tetravalent systems designed as molecular probes and synthesized by way of Cu(I)-catalysed azide-alkyne cycloadditions are fluorescent analogues of potent pharmacological chaperones/correctors recently reported in the field of Gaucher disease and cystic fibrosis, two rare genetic diseases caused by protein misfolding.

| S-EPMC4464267 | biostudies-literature

Synthesis and Glycosidase Inhibition Properties of Calix[8]arene-Based Iminosugar Click Clusters.

Project description:A set of 6- to 24-valent clusters was constructed with terminal deoxynojirimycin (DNJ) inhibitory heads through C6 or C9 linkers by way of Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reactions between mono- or trivalent azido-armed iminosugars and calix[8]arene scaffolds differing in their valency and their rigidity but not in their size. The power of multivalency to upgrade the inhibition potency of the weak DNJ inhibitor (monovalent DNJ Ki being at 322 and 188 µM for C6 or C9 linkers, respectively) was evaluated on the model glycosidase Jack Bean α-mannosidase (JBα-man). Although for the clusters with the shorter C6 linker the rigidity of the scaffold was essential, these parameters had no influence for clusters with C9 chains: all of them showed rather good relative affinity enhancements per inhibitory epitopes between 70 and 160 highlighting the sound combination of the calix[8]arene core and the long alkyl arms. Preliminary docking studies were performed to get insights into the preferred binding modes.

| S-EPMC7694328 | biostudies-literature

N-Alkylated Iminosugar Based Ligands: Synthesis and Inhibition of Human Lysosomal β-Glucocerebrosidase.

Project description:The scope of a series of N-alkylated iminosugar based inhibitors in the d-gluco as well as d-xylo configuration towards their interaction with human lysosomal β-glucocerebrosidase has been evaluated. A versatile synthetic toolbox has been developed for the synthesis of N-alkylated iminosugar scaffolds conjugated to a variety of terminal groups via a benzoic acid ester linker. The terminal groups such as nitrile, azide, alkyne, nonafluoro-tert-butyl and amino substituents enable follow-up chemistry as well as visualisation experiments. All compounds showed promising inhibitory properties as well as selectivities for β-glucosidases, some exhibiting activities in the low nanomolar range for β-glucocerebrosidase.

| S-EPMC7594070 | biostudies-literature

Prediction of inter-residue contact clusters from hydrophobic cores.

Project description:A contact map is a key factor representing a specific protein structure. To simplify the protein contact map prediction, we predict the inter-residue contact clusters centered at the groups of their surrounding inter-residue contacts. In this paper, we adopt a Support Vector Machine (SVM)-based approach to predict the inter-residue contact cluster centers. The input of the SVM predictor includes sequence profile, evolutionary rate and predicted secondary structure. The SVM predictor is based on hydrophobic cores that may be considered as locations of the inter-residue contact clusters. About 35% of clustering centers of inter-residue contacts can be predicted accurately.

| S-EPMC2929137 | biostudies-literature

A family of lead clusters with precious metal cores.

Project description:Gold nanoparticles have been used for centuries, both for decoration and in medical applications. More recently, many of the major advances in cluster chemistry have involved well-defined clusters containing tens or hundreds of atoms, either with or without a ligand shell. In this paper we report the synthesis of two gold/lead clusters, [Au8Pb33]6- and [Au12Pb44]8-, both of which contain nido [Au@Pb11]3- icosahedra surrounding a core of Au atoms. Analogues of these large clusters are not found in the corresponding Ag chemistry: instead, the Ag-centered nido icosahedron, [Ag@Pb11]3-, is the only isolated product. The structural chemistry, along with the mass spectrometry which shows the existence of [Au2Pb11]2- but not [Ag2Pb11]2-, leads us to propose that the former species is the key intermediate in the growth of the larger clusters. Density functional theory indicates that secondary π-type interactions between the [Au@Pb11]3- ligands and the gold core play a significant part in stabilizing the larger clusters.

| S-EPMC7351731 | biostudies-literature

Oligolysine-based saccharide clusters: synthesis and specificity.

Project description:In search of specific and highly selective sugar clusters for cell receptors, such as membrane lectins, various disaccharides were coupled to small peptide cores through an amide bond. In a first step, the reducing disaccharides, i.e. lactose and three different dimannoses, were converted into glycosyl-pyroglutamyl-beta-alanine derivatives. The free carboxylic group of these conjugates was then coupled to the alpha and epsilon amino groups of the core peptide (Lys( n )-Ala-Cys-NH2) with n =1 to 5, with complete substitution leading to homogeneous glycoclusters. The thiol group of the cysteine residue was used to tag the glycosylated oligolysines upon reaction with fluorescein iodoacetamide. The affinity of these glycoclusters towards two plant lectins was assessed by surface plasmon resonance. The selectivity of their cell uptake was investigated by flow cytometry using two types of cells: a human hepatoma cell line (HepG2 cells) expressing the plasma membrane galactose-specific lectin, and monocyte-derived dendritic cells expressing the plasma membrane mannose-specific lectin. The glycoclusters containing four or five disaccharides were shown to bind plant lectins and cell surface membrane lectins with a narrow selectivity and with a high affinity.

| S-EPMC1222954 | biostudies-other

Phase separation of multicomponent peptide mixtures into dehydrated clusters with hydrophilic cores.

Project description:Phase separation of biomolecules underlies the formation and regulation of various membraneless condensates in cells. How condensates function reliably while surrounded by heterogeneous and dynamic mixtures of biomolecular components with specific and nonspecific interactions is yet to be understood. Studying multicomponent biomolecular mixtures with designer peptides has recently become an attractive avenue for learning about physicochemical principles governing cellular condensates. In this work, we employed long-timescale atomistic simulations of multicomponent tripeptide mixtures with all residue substitutions to illuminate the nature of direct and water-mediated interactions in a prototypical cellular condensate environment. We find that peptide mixtures form clusters with inverse hydrophobic order. Most multivalent and charged residues are localized in the cluster's core, with a large fraction of nonaromatic hydrophobic residues remaining on the surface. This inverse hydrophobic order in peptide clusters is partly driven by the expulsion of nonspecifically bound water molecules following peptide cluster growth. The growth of clusters is also accompanied by the formation of increasing numbers of specific water-mediated interactions between polar and charged residues. While the present study focused on the condensation of short peptide motifs, the general findings and analysis techniques should be helpful for future studies on larger peptides and protein condensation.

| S-EPMC10870168 | biostudies-literature

An Amination-Cyclization Cascade Reaction for Iminosugar Synthesis Using Minimal Protecting Groups.

Project description:The development of a one-step amination-cyclization cascade reaction for the synthesis of N-substituted iminosugars from iodo-pentoses and hexoses is reported. This novel methodology allows for the stereoselective conversion of easily accessible iodo-aldoses and iodo-ketoses into iminosugars in a single step, in highly efficient yields (63-95%), and in aqueous media. Furthermore, the use of functionalized amines allows for the synthesis of N-functionalized iminosugars without additional steps. To illustrate this methodology, a number of biologically important iminosugars were prepared, including 1-deoxynojirimycin, (3S,4R,5S,6R)-azepane-3,4,5,6-tetraol, and N-functionalized 1-deoxymannojirimycins.

| S-EPMC9404175 | biostudies-literature

Atomically precise silver-based bimetallic clusters for electrocatalytic urea synthesis.

Project description:Electrocatalytic urea synthesis from CO2 and nitrate holds immense promise as a sustainable strategy, but its complicated synthesis steps and controversial C-N coupling mechanism restrict the design of efficient catalysts. Atomically precise metal cluster materials are ideal model catalysts for investigating the C-N coupling issues. Here we synthesize two atomically precise bimetallic clusters, Ag14Pd(PTFE)6(TPP)8 and Ag13Au5(PTFE)10(DPPP)4, both with icosahedral cores and similar ligands. We demonstrate that both clusters have good performance for electrocatalytic urea synthesis, with the production rates at the maximum Faradaic efficiency of 143.3 and 82.3 mg h-1 gcat -1, respectively. Bimetallic structures can induce charge polarization at the active sites of metal clusters, thereby influencing the selectivity. In mechanistic investigations, we propose that *NOH and *COOH are the rate-limiting steps for the reduction of nitrate and CO2, respectively, and that the key intermediates formed thereafter can significantly affect the C-N coupling process. This approach offers a deep understanding into C-N coupling through the utilization of atomically precise metal clusters.

| S-EPMC11740507 | biostudies-literature

Photoassisted diversity-oriented synthesis: accessing 2,6-epoxyazocane (oxamorphan) cores.

Project description:The modular synthesis of photoprecursors and their photoinduced cyclization into substituted 1-benzazocanes of two distinct topologies is described. The key step producing an extended polyheterocyclic system involves the photogeneration of azaxylylenes and their subsequent intramolecular cycloaddition with furan-containing pendants tethered either via the aniline nitrogen or through the carbonyl group containing arm. The primary photoproducts-secondary or tertiary anilines which are not acylated at the nitrogen atom-undergo facile acid-catalyzed or spontaneous ring-opening-ring-closing rearrangement to yield fused polyheterocyclic structures possessing a 2,6-epoxyazocane (or oxamorphan) core.

| S-EPMC4242042 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data