Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors.

ABSTRACT: In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten-Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz (1)H NMR spectroscopy to ensure full conversion and to use a refined neutralization and purification protocol. Many of the compounds could not be tested as L-selectin inhibitor by SPR due to their insolubility in water, nevertheless, a divalent and a trivalent amide showed surprisingly good activities with IC50 values in the low micromolar range.

SUBMITTER: Salta J

PROVIDER: S-EPMC4464473 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis of multivalent carbohydrate mimetics with aminopolyol end groups and their evaluation as L-selectin inhibitors.

Salta Joana J Dernedde Jens J Reissig Hans-Ulrich HU

Beilstein journal of organic chemistry 20150505

In this article a series of divalent and trivalent carbohydrate mimetics on the basis of an enantiopure aminopyran and of serinol is described. These aminopolyols are connected by amide bonds to carboxylic acid derived spacer units either by Schotten-Baumann acylation or by coupling employing HATU as reagent. The O-sulfation employing the SO3·DMF complex was optimized. It was crucial to follow this process by 700 MHz (1)H NMR spectroscopy to ensure full conversion and to use a refined neutraliza ...[more]

PMID: 26124866

Similar Datasets

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics.

Project description:New compounds with carbohydrate-similar structure (carbohydrate mimetics) are presented in this article. Starting from enantiopure nitrones and lithiated TMSE-allene we prepared three 1,2-oxazine derivatives which underwent a highly stereoselective Lewis acid-induced rearrangement to give bicyclic products in good yield. Subsequent reductive transformations delivered a library of new poly(hydroxy)aminooxepane derivatives. The crucial final palladium-catalyzed hydrogenolysis of the 1,2-oxazine moiety was optimized resulting in a reasonably efficient approach to a series of new seven-membered carbohydrate mimetics.

| S-EPMC3943604 | biostudies-other

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics.

Project description:An approach to β-D-2-aminotalose- and β-D-2-aminoidose-configured carbohydrate mimetics bearing a phenyl substituent is described. Unnatural divalent rigid p-terphenyl-linked C-aryl glycosides with 2.0 nm dimension are available using Suzuki cross-couplings. The key compound, a p-bromophenyl-substituted 1,2-oxazine, was prepared by a stereoselective [3 + 3]-cyclization of a D-isoascorbic acid-derived (Z)-nitrone and lithiated TMSE-allene. The Lewis acid-induced rearrangement of this heterocycle provided the corresponding bicyclic 1,2-oxazine derivative that may be regarded as internally protected amino sugar analogue. After subsequent reduction of the carbonyl group, the resulting bicyclic compound was used for Suzuki cross-couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N-O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers.

| S-EPMC4142845 | biostudies-literature

Multivalent dendritic polyglycerolamine with arginine and histidine end groups for efficient siRNA transfection.

Project description:The success of siRNA-based therapeutics highly depends on a safe and efficient delivery of siRNA into the cytosol. In this study, we post-modified the primary amines on dendritic polyglycerolamine (dPG-NH2) with different ratios of two relevant amino acids, namely, arginine (Arg) and histidine (His). To investigate the effects from introducing Arg and His to dPG, the resulting polyplexes of amino acid functionalized dPG-NH2s (AAdPGs)/siRNA were evaluated regarding cytotoxicity, transfection efficiency, and cellular uptake. Among AAdPGs, an optimal vector with (1:3) Arg to His ratio, showed efficient siRNA transfection with minimal cytotoxicity (cell viability ? 90%) in NIH 3T3 cells line. We also demonstrated that the cytotoxicity of dPG-NH2 decreased as a result of amino acid functionalization. While the incorporation of both cationic (Arg) and pH-responsive residues (His) are important for safe and efficient siRNA transfection, this study indicates that AAdPGs containing higher degrees of His display lower cytotoxicity and more efficient endosomal escape.

| S-EPMC4464416 | biostudies-literature

The Synthesis and Evaluation of Multivalent Glycopeptoids as Inhibitors of the Adhesion of Candida albicans.

Project description:Multivalency is a strategy commonly used by medicinal carbohydrate chemists to increase the affinity of carbohydrate-based small molecules for their protein targets. Although this approach has been very successful in enhancing binding to isolated carbohydrate-binding proteins, anticipating the multivalent presentations that will improve biological activity in cellular assays remains challenging. In this work we investigate linear molecular scaffolds for the synthesis of a low valency presentation of a divalent galactoside 1, previously identified by us as an inhibitor of the adhesion of opportunistic fungal pathogen Candida albicans to buccal epithelial cells (BECs). Adhesion inhibition assays revealed that multivalent glycoconjugate 3 is more effective at blocking C. albicans adherence to BECs upon initial exposure to epithelial cells. Interestingly, 3 did not seem to have any effect when it was pre-incubated with yeast cells, in contrast to the original lead compound 1, which caused a 25% reduction of adhesion. In competition assays, where yeast cells and BECs were co-incubated, multivalent glycoconjugate 3 inhibited up to 49% C. albicans adherence in a dose-dependent manner. The combined effect of compound 1 towards both yeast cells and BECs allowed it to achieve over 60% inhibition of the adhesion of C. albicans to BECs in competition assays.

| S-EPMC8151480 | biostudies-literature

Triggerable Multivalent Glyconanoparticles for Probing Carbohydrate-Carbohydrate Interactions.

Project description:Carbohydrate-carbohydrate interactions are proposed to be biologically significant but have lower affinities than the well-studied carbohydrate-protein interactions. Here we introduce multivalent glyconanostructures where the surface expression of lactose can be triggered by an external stimulus, and a gold nanoparticle core enables colorimetric signal outputs to probe binding. Macromolecular engineering of a responsive polymer "gate" enables the lactose moieties to be presented only when an external stimulus is present, mimicking how nature uses enzymes to dynamically regulate glycan expression. Two different carbohydrate-carbohydrate interactions are investigated using this tool.

| S-EPMC5894439 | biostudies-literature

Synthesis of new lophine-carbohydrate hybrids as cholinesterase inhibitors: cytotoxicity evaluation and molecular modeling.

Project description:In this study, we synthesized nine novel hybrids derived from d-xylose, d-ribose, and d-galactose sugars connected by a methylene chain with lophine. The compounds were synthesized by a four-component reaction to afford the substituted imidazole moiety, followed by the displacement reaction between sugar derivatives with an appropriate N-alkylamino-lophine. All the compounds were found to be the potent and selective inhibitors of BuChE activity in mouse serum, with compound 9a (a d-galactose derivative) being the most potent inhibitor (IC50 = 0.17 μM). According to the molecular modeling results, all the compounds indicated that the lophine moiety existed at the bottom of the BuChE cavity and formed a T-stacking interaction with Trp231, a residue accessible exclusively in the BuChE cavity. Noteworthily, only one compound exhibited activity against AChE (8b; IC50 = 2.75 μM). Moreover, the in silico ADME predictions indicated that all the hybrids formulated in this study were drug-likely, orally available, and able to reach the CNS. Further, in vitro studies demonstrated that the two most potent compounds against BuChE (8b and 9a) had no cytotoxic effects in the Vero (kidney), HepG2 (hepatic), and C6 (astroglial) cell lines.

| S-EPMC7451069 | biostudies-literature

Exploring multivalent carbohydrate-protein interactions by NMR.

Project description:Nuclear Magnetic Resonance (NMR) has been widely employed to assess diverse features of glycan-protein molecular recognition events. Different types of qualitative and quantitative information at different degrees of resolution and complexity can be extracted from the proper application of the available NMR-techniques. In fact, affinity, structural, kinetic, conformational, and dynamic characteristics of the binding process are available. Nevertheless, except in particular cases, the affinity of lectin-sugar interactions is weak, mostly at the low mM range. This feature is overcome in biological processes by using multivalency, thus augmenting the strength of the binding. However, the application of NMR methods to monitor multivalent lectin-glycan interactions is intrinsically challenging. It is well known that when large macromolecular complexes are formed, the NMR signals disappear from the NMR spectrum, due to the existence of fast transverse relaxation, related to the large size and exchange features. Indeed, at the heart of the molecular recognition event, the associated free-bound chemical exchange process for both partners takes place in a particular timescale. Thus, these factors have to be considered and overcome. In this review article, we have distinguished, in a subjective manner, the existence of multivalent presentations in the glycan or in the lectin. From the glycan perspective, we have also considered whether multiple epitopes of a given ligand are presented in the same linear chain of a saccharide (i.e., poly-LacNAc oligosaccharides) or decorating different arms of a multiantennae scaffold, either natural (as in multiantennae N-glycans) or synthetic (of dendrimer or polymer nature). From the lectin perspective, the presence of an individual binding site at every monomer of a multimeric lectin may also have key consequences for the binding event at different levels of complexity.

| S-EPMC9987413 | biostudies-literature

Synthesis and evaluation of in vitro bioactivity for vesicular acetylcholine transporter inhibitors containing two carbonyl groups.

Project description:To identify selective high-affinity ligands for the vesicular acetylcholine transporter (VAChT), we have incorporated a carbonyl group into the structures of trozamicol and prezamicol scaffolds, and also converted the secondary amines of the piperidines of trozamicols and prezamicols into amides. Of 18 new racemic compounds, 4 compounds displayed high affinity for VAChT (K(i)=10-20 nM) and greater than 300-fold selectivity for VAChT over ?(1) and ?(2) receptors, namely (4-(4-fluorobenzoyl)-4'-hydroxy-[1,3'-bipiperidin]-1'-yl)(3-methylthiophen-2-yl)methanone oxalate (9g) (K(i-VAChT)=11.4 nM, VAChT/?(1)=1063, VAChT/?(2)=370), (1'-benzoyl-4'-hydroxy-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10c) (K(i-VAChT)=15.4 nM, VAChT/?(1)=374, VAChT/?(2)=315), (4'-hydroxy-1'-(thiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10e) (K(i-VAChT)=19.0 nM, VAChT/?(1)=1787, VAChT/?(2)=335), and (4'-hydroxy-1'-(3-methylthiophene-2-carbonyl)-[1,3'-bipiperidin]-4-yl)(4-methoxyphenyl)methanone oxalate (10g) (K(i-VAChT)=10.2 nM, VAChT/?(1)=1500, VAChT/?(2)=2030). These four compounds can be radiosynthesized with C-11 or F-18 to validate their possibilities of serving as PET probes for quantifying the levels of VAChT in vivo.

| S-EPMC3389281 | biostudies-literature

Multivalent interaction-based carbohydrate biosensors for signal amplification.

Project description:Multivalent interaction between boronic acids immobilized on quartz crystal microbalance (QCM) sensor surface and the carbohydrates modified Au-nanoparticle (AuNP) has been demonstrated for the development of a sensitive carbohydrate biosensor. Briefly, a boronic acid-containing polymer (boropolymer) as multivalent carbohydrate receptor was oriented immobilized on the cysteamine coated electrode through isourea bond formation. Carbohydrates were conjugated to AuNPs to generate a multivalent carbohydrates moiety to amplify the response signal. Thus, the binding of the carbohydrate conjugated AuNPs to the boropolymer surface are multivalent which could simultaneously increase the binding affinity and specificity. We systematically studied the binding between five carbohydrates conjugated AuNPs and the boropolymer. Our studies show that the associate constant (K(a)) was in the order of fucose<glucose<mannose<galactose<maltose. A linear response in the range from 23 μM to 3.83 mM was observed for mannose conjugated AuNPs and the boropolymer recognition elements, with the lower detection limit of 1.5 μM for the carbohydrate analytes. Furthermore, the multivalent binding between carbohydrates and boronic acids are reversible and allow the regeneration of boropolymer surface by using 1M acetic acid so as to sequentially capture and release the carbohydrate analytes.

| S-EPMC2981037 | biostudies-literature

Gold nanoparticle-based multivalent carbohydrate probes: selective photoaffinity labeling of carbohydrate-binding proteins.

Project description:Multivalent carbohydrate photoaffinity probes were developed based on gold nanoparticles (AuNPs) to provide a streamlined approach toward identification of carbohydrate-binding proteins. By using AuNPs as scaffolds, a carbohydrate ligand and a photoreactive group could be readily assembled on a probe in a modular fashion, which greatly accelerated the process of optimizing the probe design. The novel AuNP-based probes serve dual functions by facilitating photoaffinity labeling and by directly enriching the crosslinked proteins by centrifugation. We demonstrated that their ability to enhance the affinity and to stringently remove nonspecific proteins allowed selective photoaffinity labeling and isolation of a low affinity carbohydrate-binding protein in cell lysate.

| S-EPMC5530003 | 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