Fecha de presentación internacional: 24.05.2005. - Titulares: Consejo Superior de Investigaciones... more Fecha de presentación internacional: 24.05.2005. - Titulares: Consejo Superior de Investigaciones Científicas (CSIC). - MIDATECH LTDMaterials and methods are provided for making nanoparticles having a core including metal and/or semiconductor atoms, which core is covalently linked to a plurality of ligands comprising a RNA ligand. The RNA ligands may include siRNA or miRNA. Also provided are uses of these nanoparticles in therapy and diagnosis.Peer reviewe
In exploring the scope and the limitations of glyconanoparticles to study and to intervene in bio... more In exploring the scope and the limitations of glyconanoparticles to study and to intervene in biological molecular recognition phenomena in which carbohydrates are involved, we have initiated a program on the potential of this technology to develop carbohydrate based anticancer vaccines. 7 ...
The first direct NMR determination of the conformation of a conformationally flexible heparin-lik... more The first direct NMR determination of the conformation of a conformationally flexible heparin-like hexasaccharide bound to a key receptor, FGF-1, is described. The determination has been based on the use of a 13C-labeled protein and a regular 12C sugar. FGF-1 recognizes several conformations of the iduronic moieties of the hexasaccharide. Therefore, this case is different than that described for the controversial recognition of heparin-like saccharides by AT-III, which seems to recognize just one conformation of the iduronic acid residues.
The cover picture shows a comparison of the effect of increasing concentrations of heparin and tw... more The cover picture shows a comparison of the effect of increasing concentrations of heparin and two synthetic heparin‐like hexasaccharides, with specifically designed different sulfation patterns, on the mitogenic activity of acidic fibroblast growth factor (FGF‐1). These two hexasaccharides, members of a series of six synthetic oligosaccharides with the same monosaccharide sequence but differing size and charge distribution, either have different negative charge orientations on both sides, like heparin itself, or on one side of their three dimensional helical structures. This alternative arrangement induces differences in the electrostatic potential, as is shown in the surface maps. The hexasaccharide with sulfate groups on only one side of the helix stimulates FGF‐1 more efficiently than that with the sulfate groups distributed on both sides as in the regular region of heparin. This result and the fact that, according to sedimentation‐equilibrium analysis, these oligosaccharides do...
A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently dev... more A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently developed in our laboratory. Ten different multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y) antigens, T-cell helper peptides (TT) and glucose in well defined average proportions and with differing density have been synthesised in one step and characterised using NMR and TEM. Size and nature of the linker were crucial to control kinetics of S-Au bond formation and to achieve the desired ligand ratio on the gold clusters. The technology presented here opens the way for tailoring polyvalent anticancer vaccines candidates and drug delivery carriers with defined average chemical composition.
Heparin-like hexasaccharide 3 and octasaccharide 4 have been synthesized using a convergent block... more Heparin-like hexasaccharide 3 and octasaccharide 4 have been synthesized using a convergent block strategy and their solution conformations have been determined by NMR spectroscopy. Both oligosaccharides contain the basic structural motif of the regular region of heparin but have been constructed as to display negatively charged sulfate groups only on one side of their solution helical structures. This charge distribution along the saccharide chain has been designed to get insight into the proposed mechanism for fibroblast growth factors (FGFs) activation that involves heparin-induced FGF dimerization.Key words: heparin oligosaccharides, synthesis design, conformational analysis, FGF activation.
The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF‐1) and a specifi... more The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF‐1) and a specifically designed synthetic heparin hexasaccharide has been determined by NMR spectroscopy. This hexasaccharide can substitute natural heparins in FGF‐1 mitogenesis assays, in spite of not inducing any apparent dimerization of the growth factor. The use of this well defined synthetic heparin analogue has allowed us to perform a detailed NMR structural analysis of the heparin–FGF interaction, overcoming the limitations of NMR to deal with the high molecular mass and heterogeneity of the FGF‐1 oligomers formed in the presence of natural heparin fragments. Our results confirm that glycosaminoglycans induced FGF‐1 dimerization either in a cis or trans disposition with respect to the heparin chain is not an absolute requirement for biological activity.
Fecha de presentación internacional: 24.05.2005. - Titulares: Consejo Superior de Investigaciones... more Fecha de presentación internacional: 24.05.2005. - Titulares: Consejo Superior de Investigaciones Científicas (CSIC). - MIDATECH LTDMaterials and methods are provided for making nanoparticles having a core including metal and/or semiconductor atoms, which core is covalently linked to a plurality of ligands comprising a RNA ligand. The RNA ligands may include siRNA or miRNA. Also provided are uses of these nanoparticles in therapy and diagnosis.Peer reviewe
In exploring the scope and the limitations of glyconanoparticles to study and to intervene in bio... more In exploring the scope and the limitations of glyconanoparticles to study and to intervene in biological molecular recognition phenomena in which carbohydrates are involved, we have initiated a program on the potential of this technology to develop carbohydrate based anticancer vaccines. 7 ...
The first direct NMR determination of the conformation of a conformationally flexible heparin-lik... more The first direct NMR determination of the conformation of a conformationally flexible heparin-like hexasaccharide bound to a key receptor, FGF-1, is described. The determination has been based on the use of a 13C-labeled protein and a regular 12C sugar. FGF-1 recognizes several conformations of the iduronic moieties of the hexasaccharide. Therefore, this case is different than that described for the controversial recognition of heparin-like saccharides by AT-III, which seems to recognize just one conformation of the iduronic acid residues.
The cover picture shows a comparison of the effect of increasing concentrations of heparin and tw... more The cover picture shows a comparison of the effect of increasing concentrations of heparin and two synthetic heparin‐like hexasaccharides, with specifically designed different sulfation patterns, on the mitogenic activity of acidic fibroblast growth factor (FGF‐1). These two hexasaccharides, members of a series of six synthetic oligosaccharides with the same monosaccharide sequence but differing size and charge distribution, either have different negative charge orientations on both sides, like heparin itself, or on one side of their three dimensional helical structures. This alternative arrangement induces differences in the electrostatic potential, as is shown in the surface maps. The hexasaccharide with sulfate groups on only one side of the helix stimulates FGF‐1 more efficiently than that with the sulfate groups distributed on both sides as in the regular region of heparin. This result and the fact that, according to sedimentation‐equilibrium analysis, these oligosaccharides do...
A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently dev... more A novel platform for anticancer vaccines has been prepared using glyconanotechnology recently developed in our laboratory. Ten different multifunctional gold glyconanoparticles incorporating sialylTn and Lewis(y) antigens, T-cell helper peptides (TT) and glucose in well defined average proportions and with differing density have been synthesised in one step and characterised using NMR and TEM. Size and nature of the linker were crucial to control kinetics of S-Au bond formation and to achieve the desired ligand ratio on the gold clusters. The technology presented here opens the way for tailoring polyvalent anticancer vaccines candidates and drug delivery carriers with defined average chemical composition.
Heparin-like hexasaccharide 3 and octasaccharide 4 have been synthesized using a convergent block... more Heparin-like hexasaccharide 3 and octasaccharide 4 have been synthesized using a convergent block strategy and their solution conformations have been determined by NMR spectroscopy. Both oligosaccharides contain the basic structural motif of the regular region of heparin but have been constructed as to display negatively charged sulfate groups only on one side of their solution helical structures. This charge distribution along the saccharide chain has been designed to get insight into the proposed mechanism for fibroblast growth factors (FGFs) activation that involves heparin-induced FGF dimerization.Key words: heparin oligosaccharides, synthesis design, conformational analysis, FGF activation.
The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF‐1) and a specifi... more The 3D structure of a complex formed by the acidic fibroblast growth factor (FGF‐1) and a specifically designed synthetic heparin hexasaccharide has been determined by NMR spectroscopy. This hexasaccharide can substitute natural heparins in FGF‐1 mitogenesis assays, in spite of not inducing any apparent dimerization of the growth factor. The use of this well defined synthetic heparin analogue has allowed us to perform a detailed NMR structural analysis of the heparin–FGF interaction, overcoming the limitations of NMR to deal with the high molecular mass and heterogeneity of the FGF‐1 oligomers formed in the presence of natural heparin fragments. Our results confirm that glycosaminoglycans induced FGF‐1 dimerization either in a cis or trans disposition with respect to the heparin chain is not an absolute requirement for biological activity.
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Papers by Rafael HD Ojeda