1,721,063 research outputs found
Modulation of the biological function of a synthetic carbohydrate antigen related to Streptococcus pneumoniae infections
No full textCD1 Glycosphingolipid Antigen Synthesis for the Study of Protein-Carbohydrate Interactions
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Sintesi di neoglicosfingolipidi modificati nella lunghezza e nella natura della base sfingoide
No full textSynthesis of photoactivable probes for the study of glycosphingolipid-protein interactions
No full textSYNTHESIS OF PHOTOACTIVABLE PROBES FOR THE STUDY OF GLYCOSPHINGOLIPID-PROTEIN INTERACTIONS
Giuseppina Brasile,1 Federica Compostella,1 Laura Mauri,2Sandro Sonnino2 and Fiamma Ronchetti1
Dipartimento di Chimica, Biochimica e Biotecnologie per la Medicina, Università di Milano
1Via Saldini 50, 20133-Milano, Italy; 2Via Fratelli Cervi 93, 20190- Segrate (Milano), Italy
E-mail:[email protected]
It is widely accepted that glycosphingolipids (GSLs) at the level of the plasma membrane can affect the biological functions of protein molecules, such as cell surface receptors or transporters. The interactions between GSLs and proteins belonging to specific membrane microdomains, called lipid rafts, could be responsible for the modulation of the functional properties of membrane proteins participating in signal transduction. GSL-protein interactions can be investigated by cell photolabelling experiments using radioactive photoactivable GSLs, which yield, when illuminated, a very reactive intermediate that covalently binds to the molecules in the environment, i.e. proteins.1,2
In this context, we have designed a fatty acid probe with two nitrophenylazide photoactivable groups, one at position 2 and the other at the end of the acyl chain. The conjugation of the fatty acid to a radioactive sphingoglycolipid generates a species to be used for photolabelling experiments. In this way, the simultaneous identification of the proteins belonging to both the leaflets of the plasma membrane, the cytoplasmatic and the extracellular one, will be realized.
Herein we describe a general synthetic strategy to obtain not commercially available α,ω-diamino acids, the synthetic precursors of the labelled fatty acids, which we have applied to the synthesis of a C-18 derivative. Furthermore, it will be described the preparation of a photolabelled radioactive GSL as a case study.
1. Aureli M., Prioni S., Mauri L. Loberto N., Casellato R., Ciampa M.G., Chigorno V., Prinetti, A.; Sonnino S. J. Lipid Res. 2010, 51, 798-808
2. Mauri L., Prioni S., Loberto N., Chigorno V., Prinetti A., Sonnino S. Glycoconj. J. 2004, 20, 11-23
Synthesis and Modeling of alpha Dimethylated (alpha-L-Rhamnopyranosyl)Methylphosphonic Acid
No full textThe capsular polysaccharide Vi from Salmonella typhi: synthesis and molecular dynamic simulations of short analogue fragments
No full textVi capsular polysaccharide (Vi antigen) is the virulence factor of Salmonella enterica serovar typhi, the causative agent of typhoid fever in humans. It is a linear homopolymer made up of alpha-(1→4)-linked N-acetyl galactosaminuronic acid with a 60-70% O-acetylation at C-3. Vaccination with purified Vi antigen from Salmonella typhi can protect against typhoid fever, although many aspects of the mechanism of action have yet to be established. It has been demonstrated that the immunogenicity of Vi is strongly related to the content of O-acetyl groups and seems not related to the presence of the carboxyl groups. In fact, the acetate groups dominate the molecular surface of the polysaccharide and confer hydrophobic properties to it, probably shielding the carboxylic groups from interaction with other molecules, even if only partial 3-O-acetylation seems necessary to maintain the flexibility of the molecules. Being interested in the study of the role of the negative charge of the Vi biopolymer on the biological activity, we have planned the preparation of analogues where the carboxylic group has been substituted with a pH-independent ionizable group, i.e. the sulfate group. The sulfate group has been selected after preliminary investigations through molecular dynamics simulations on a hexasaccharide Vi antigen fragment, that showed similarities between the conformational behavior of the natural antigen and the sulfate analogue, where the galacturonic residues have been replaced with 6-O-sulfo-galactoses.
Herein we will report our results on the conformational analysis and the stereoselective synthesis of Vi antigen sulfated-analogue fragments
An Efficient Transformation of (-)-Quinic Acid into Carba-L-Rhamnose
No full textA novel stereoselective synthesis of carba-L-rhamnose from (-)-quinic acid is described. The title compound is obtained with an appropriate pattern of protecting groups to be used for the preparation of Streptococcus pneumoniae type 19F capsular polysaccharide repeating unit
Photoactivable probes for the study of glycosphingolipid-protein interactions in lipid-rich membrane domains
No full textLipid-rafts are membrane microdomains particularly enriched in glycosphingolipids (GSLs) involved in the information transduction process across the membrane.
The great interest for such domains is due to the observation that some membrane associated proteins are highly concentrated in lipid rafts, even if the overall protein content of these membrane areas is very low. It has been assumed that the trapping of certain proteins in lipid rafts might be somehow functional to their biological role, i.e. their involvement in signal transduction processes.
GSL-protein interactions can be investigated by cell photolabelling experiments using radioactive photoactivable GSLs, which yield, when illuminated, a very reactive intermediate that covalently binds to the molecules in the environment, i.e. proteins.
In this context, we have designed a fatty acid probe with two nitrophenylazide photoactivable groups, one at position 2 and the other at the end of the acyl chain. The conjugation of the fatty acid to a radioactive glycosphingolipid generates a species to be used for photolabelling experiments allowing the simultaneous identification of the proteins belonging to the cytoplasmatic and the extracellular leaflets of the membrane. Herein we describe a general synthetic strategy to obtain not commercially available α,ω-diamino acids, the synthetic precursors of the labelled fatty acids, which we have applied to the synthesis of a C-18 derivative. Furthermore, it will be described the preparation of a photolabelled radioactive GSL as a case study
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