Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Synthesis and evaluation of amino-modified alpha-GalCer analogues.

ABSTRACT: Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3- and 4-positions of suitable phytosphingosine-derived precursors. The influence of these modifications on the interaction with the T-cell receptor of NKT cells was investigated, as well as the capacity of the amino-modified analogues to induce a cytokine response after in vivo administration.

SUBMITTER: Trappeniers M

PROVIDER: S-EPMC2903208 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Synthesis and evaluation of amino-modified alpha-GalCer analogues.

Trappeniers Matthias M Chofor René R Aspeslagh Sandrine S Li Yali Y Linclau Bruno B Zajonc Dirk M DM Elewaut Dirk D Van Calenbergh Serge S

Organic letters 20100701 13

Alpha-GalCer analogues featuring a phytoceramide 3- and 4-amino group have been synthesized. A Mitsunobu reaction involving phthalimide was employed for the introduction of the amino groups at the 3- and 4-positions of suitable phytosphingosine-derived precursors. The influence of these modifications on the interaction with the T-cell receptor of NKT cells was investigated, as well as the capacity of the amino-modified analogues to induce a cytokine response after in vivo administration. ...[more]

PMID: 20518554

Similar Datasets

Design, Synthesis, and Immunological Evaluation of Benzyloxyalkyl-Substituted 1,2,3-Triazolyl α-GalCer Analogues.

Project description:Replacement of the amide moiety in the structure of α-GalCer with a 1,2,3-triazole linker is known to elicit a response skewed toward Th2 immunity, and glycolipids containing an aromatic ring in the terminus of their acyl or phytosphingosine structural component exhibit an enhanced Th1 immune response. In the current study, synthesis and immunological screening of a focused library of benzyloxyalkyl-substituted 1,2,3-triazolyl α-GalCer analogues are reported. The novel α-GalCer analogues activate invariant natural killer T (iNKT) cells via CD1d mediated presentation, which was confirmed by in vitro tests performed on iNKT hybridomas incubated with CD1d proteins. When tested on isolated murine splenocytes, the T1204B and T1206B compounds stimulated higher levels of both IFN-γ and IL-4 cytokine expression in vitro compared to that of α-GalCer.

| S-EPMC4753537 | biostudies-literature

Divergent synthetic approach to 6''-modified ?-GalCer analogues.

Project description:A synthetic approach is presented for the synthesis of galacturonic acid and D-fucosyl modified KRN7000. The approach allows for late-stage functionalisation of both the sugar 6''-OH and the sphingosine amino groups, which enables convenient synthesis of promising 6''-modified KRN7000 analogues.

| S-EPMC3246390 | biostudies-literature

Alpha-S-GalCer: synthesis and evaluation for iNKT cell stimulation.

Project description:The synthesis and evaluation for iNKT stimulation of alpha-S-galactosylceramide is reported. Prepared by alkylation of a galactosylthiol, this analog of the potent immunostimulatory agent, KRN7000, did not stimulate iNKT cells either in vitro or in vivo.

| S-EPMC2628538 | biostudies-literature

Design and Evaluation of ω-Hydroxy Fatty Acids Containing α-GalCer Analogues for CD1d-Mediated NKT Cell Activation.

Project description:CD1d molecules recognize glycolipid antigens with straight chain fatty acid moieties. Although most of the residues in the CD1d binding groove are hydrophobic, some of the amino acids can form hydrogen bonds. Consequently, we have designed ω-hydroxy fatty acid-containing glycolipid derivatives of the prototypical CD1d ligand α-GalCer. The potency of the ω-hydroxy analogues of the proper length is comparable to that of α-GalCer. We propose, based on the biological results and molecular modeling studies, that a hydrogen bonding interaction is involved between the ω-hydroxy group and a polar amino acid residue in the hydrophobic binding groove.

| S-EPMC4027640 | biostudies-literature

Galactosylsphingamides: new α-GalCer analogues to probe the F'-pocket of CD1d.

Project description:Invariant Natural Killer T-cells (iNKT-cells) are an attractive target for immune response modulation, as upon CD1d-mediated stimulation with KRN7000, a synthetic α-galactosylceramide, they produce a vast amount of cytokines. Here we present a synthesis that allows swift modification of the phytosphingosine side chain by amidation of an advanced methyl ester precursor. The resulting KRN7000 derivatives, termed α-galactosylsphingamides, were evaluated for their capacity to stimulate iNKT-cells. While introduction of the amide-motif in the phytosphingosine chain is tolerated for CD1d binding and TCR recognition, the studied α-galactosylsphingamides showed compromised antigenic properties.

| S-EPMC5487351 | biostudies-literature

Synthesis and antioxidant evaluation of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters from modified α-amino acids.

Project description:The efforts for synthesis of enantiomerically pure bis-(1,2,3-triazolylmethyl)amino esters 6 are reported in good yields from an in situ generated α-azidomethyl ketone. Optimum experimental conditions were established for preparation of α-halomethyl ketones 10 and α-N,N-dipropargylamino esters 11, all derived from α-amino acids. The starting materials reacted under conventional click chemistry conditions, revealing a specific reactivity of bromomethyl ketones over chloromethyl ketones. The antioxidant activity of compounds 6 was assayed by DPPH method. The compound 6c with an IC50 of 75.57 ± 1.74 μg mL(-1) was the most active. Technically, this methodology allows the preparation of a combinatorial library of analogues with different structural characteristics depending on the nature of the modified α-amino acids employed in the synthesis.

| S-EPMC4216715 | biostudies-literature

Development of α-GalCer Analogues with an α-Fluorocarbonyl Moiety as Th2-Selective Ligands of CD1d.

Project description:A series of α-GalCer analogues containing an α-fluorocarbonyl moiety at the terminal position of the acyl chain were designed for targeting polar residues in the hydrophobic cavity of CD1d using a structure-based approach. The acyl chain length was efficiently adjusted by an asymmetric alkyne-alkyne cross coupling strategy, and the newly synthesized α-GalCer analogues showed the high Th2-selective activity of iNKT cells. The biased activity of ligands could be caused by the hydrogen-bonding interaction between ligands and CD1d according to the Th2-selective cytokine secretion and molecular docking studies.

| S-EPMC6511957 | biostudies-literature

Efficient Divergent Synthesis of New Immunostimulant 4″-Modified α-Galactosylceramide Analogues.

Project description:A synthesis strategy for the swift generation of 4″-modified α-galactosylceramide (α-GalCer) analogues is described, establishing a chemical platform to comprehensively investigate the structure-activity relationships (SAR) of this understudied glycolipid part. The strategy relies on a late-stage reductive ring-opening of a p-methoxybenzylidene (PMP) acetal to regioselectively liberate the 4″-OH position. The expediency of this methodology is demonstrated by the synthesis of a small yet diverse set of analogues, which were tested for their ability to stimulate invariant natural killer T-cells (iNKT) in vitro and in vivo. The introduction of a p-chlorobenzyl ether yielded an analogue with promising immunostimulating properties, paving the way for further SAR studies.

| S-EPMC5467197 | biostudies-literature

Synthesis and Cytotoxicity Evaluation of C4- and C5-Modified Analogues of the α,β-Unsaturated Lactone of Pironetin.

Project description:Pironetin is a natural product with potent antiproliferative activity that forms a covalent adduct with α-tubulin via conjugate addition into the natural product's α,β-unsaturated lactone. Although pironetin's α,β-unsaturated lactone is involved in its binding to tubulin, the structure-activity relationship at different positions of the lactone have not been thoroughly evaluated. For a systematic evaluation of the structure-activity relationships at the C4 and C5 positions of the α,β-unsaturated lactone of pironetin, twelve analogues of the natural product were prepared by total synthesis. Modifying the stereochemistry at the C4 and/or C5 positions of the α,β-unsaturated lactone of pironetin resulted in loss of antiproliferative activity in OVCAR5 ovarian cancer cells. While changing the C4 ethyl substituent with groups such as methyl, propyl, cyclopropyl, and isobutyl were tolerated, groups with larger steric properties such as an isopropyl and benzyl groups were not.

| S-EPMC5413833 | biostudies-literature

Synthesis and evaluation of α-thymidine analogues as novel antimalarials.

Project description:Plasmodium falciparum thymidylate kinase (PfTMPK) is a key enzyme in pyrimidine nucleotide biosynthesis. 3-Trifluoromethyl-4-chloro-phenyl-urea-α-thymidine has been reported as an inhibitor of Mycobacterium tuberculosis TMPK (MtTMPK). Starting from this point, we designed, synthesized and evaluated a number of thymidine analogues as antimalarials. Both 5'-urea-α- and β-thymidine derivatives were moderate inhibitors of PfTMPK and furthermore showed moderate inhibition of parasite growth. The structure of several enzyme-inhibitor complexes provides a basis for improved inhibitor design. However, we found that certain 5'-urea-α-thymidine analogues had antimalarial activity where inhibition of PfTMPK is not the major mode of action. Optimization of this series resulted in a compound with potent antimalarial activity (EC(50) = 28 nM; CC(50) = 29 μM).

| S-EPMC3530961 | 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