The Experts below are selected from a list of 702 Experts worldwide ranked by ideXlab platform

Samuel J Danishefsky - One of the best experts on this subject based on the ideXlab platform.

  • toward fully synthetic homogeneous β human follicle stimulating hormone β hfsh with a biantennary n linked dodecasaccharide synthesis of β hfsh with chitobiose units at the natural linkage sites
    Journal of the American Chemical Society, 2009
    Co-Authors: Pavel Nagorny, Samuel J Danishefsky, Baptiste Aussedat, Bernhard Fasching, Gong Chen
    Abstract:

    A highly convergent synthesis of the sialic acid-rich biantennary N-linked glycan found in human glycoprotein hormones and its use in the synthesis of a fragment derived from the β-domain of human Follicle-Stimulating Hormone (hFSH) are described. The synthesis highlights the use of the Sinay radical glycosidation protocol for the simultaneous installation of both biantennary side-chains of the dodecasaccharide as well as the use of Glycal chemistry to construct the tetrasaccharide core in an efficient manner. The synthetic glycan was used to prepare the glycosylated 20−27aa domain of the β-subunit of hFSH under a Lansbury aspartylation protocol. The proposed strategy for incorporating the prepared N-linked dodecasaccharide-containing 20−27aa domain into β-hFSH subunit was validated in the context of a model system, providing protected β-hFSH subunit functionalized with chitobiose at positions 7 and 24.

  • design and synthesis of ley bearing glycopeptides that mimic cell surface ley mucin glycoprotein architecture
    Journal of the American Chemical Society, 2000
    Co-Authors: Peter W Glunz, Samuel Hintermann, Lawrence J Williams, Jacob B Schwarz, Scott D Kuduk, Valery Kudryashov, And Kenneth O Lloyd, Samuel J Danishefsky
    Abstract:

    Five Lewisy-based glycopeptide anti-cancer vaccine candidates have been designed and synthesized to target tumor-associated cell-surface glycoprotein antigens and to improve the immunizing performance in comparison to related vaccines. The peptide backbone consisted of two regions, a glycodomain AcNH-SSS- and a nonglycosylated sequence, -AVAV-. The resultant glycopeptide was conjugated, via an additional spacer, to the lipid carrier PamCysSer. In this series of totally synthetic molecular vaccine candidates, one or three of the sequentially arranged serine residues were glycosylated. Furthermore, the Ley tetrasaccharide determinant region was kept constant while the internal glycan core was systematically varied. Glycal assembly was used to prepare the glycosyl donors, and two strategies were applied to provide the serine-O-linked polysaccharide domains. In the first approach, a protected serine derivative was attached directly to the fully elaborated glycan. Following this course, both α- and β-Ser deriv...

  • Glycals in organic synthesis the evolution of comprehensive strategies for the assembly of oligosaccharides and glycoconjugates of biological consequence
    Angewandte Chemie, 1996
    Co-Authors: Samuel J Danishefsky, M T Bilodeau
    Abstract:

    This review provides a personal account of the explorations of a research group in oligosaccharide and glycoconjugate construction. The journey began twenty years ago with the study of Diels–Alder reactions of complex dienes. By extending this methodology to aldehydo-type heterodienophile equivalents, access to unnatural Glycals was gained (LACDAC reaction). From this point a broad-ranging investigation of the use of Glycals in the synthesis of oligosaccharides and other glycoconjugates was begun. Mobilization of Glycals both as glycosyl donors and glycosyl acceptors led to the strategy of Glycal assembly. Several new glycosylation techniques were developed to provide practical underpinning for this logic of Glycal assembly. Glycal-based paradigms have been shown to be nicely adaptable to solid phase supported synthesis. Moreover, Glycal assembly—both in solution and on solid phases—has been used to gain relatively concise and efficient entry to a variety of biologically interesting and potentially valuable constructs. Some of these syntheses, particularly in the field of tumor antigens, have led to novel compounds which are in the final stages of preclinical assessment. This review presents an account of the chemical reasoning at the center of the program.

  • staurosporine and ent staurosporine the first total syntheses prospects for a regioselective approach and activity profiles1
    Journal of the American Chemical Society, 1996
    Co-Authors: J. T. Link, Subharekha Raghavan, Michel Gallant, Tingchau Chou, Samuel J Danishefsky, Lawrence M Ballas
    Abstract:

    The total syntheses of staurosporine and ent-staurosporine have been achieved. Both glycosidic bonds were built from Glycal precursors. The first was constructed by intermolecular coupling of an indole anion with a 1,2-anhydrosugar derived from an endo-Glycal by direct epoxidation. The second bond was assembled from an exo-Glycal by intramolecular iodoglycosylation.

Samia Mora - One of the best experts on this subject based on the ideXlab platform.

  • circulating n linked glycoprotein side chain biomarker rosuvastatin therapy and incident cardiovascular disease an analysis from the jupiter trial
    Journal of the American Heart Association, 2016
    Co-Authors: Akintunde O Akinkuolie, Robe J Gly, Latha Padmanabha, Paul M Ridke, Samia Mora
    Abstract:

    Background GlycA, a novel protein glycan biomarker of N ‐acetyl side chains of acute‐phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. Methods and Results In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low‐density lipoprotein cholesterol 0.20). Conclusion In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. Clinical Trials Registration URL: . Unique identifier: NCT00239681.

  • circulating n linked glycoprotein side chain biomarker rosuvastatin therapy and incident cardiovascular disease an analysis from the jupiter trial
    Journal of the American Heart Association, 2016
    Co-Authors: Akintunde O Akinkuolie, Robert J Glynn, Latha Padmanabhan, Paul M Ridker, Samia Mora
    Abstract:

    Background GlycA, a novel protein glycan biomarker of N ‐acetyl side chains of acute‐phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. Methods and Results In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low‐density lipoprotein cholesterol 0.20). Conclusion In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. Clinical Trials Registration URL: . Unique identifier: NCT00239681.

  • novel protein glycan side chain biomarker and risk of incident type 2 diabetes mellitus
    Arteriosclerosis Thrombosis and Vascular Biology, 2015
    Co-Authors: Akintunde O Akinkuolie, Paul M Ridker, Julie E Buring, Aruna D Pradhan, Samia Mora
    Abstract:

    Objectives— Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N -acetyl methyl groups originating mainly from N -acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with high-sensitivity C-reactive protein. Approach and Results— In 26 508 initially healthy women free of diabetes mellitus, baseline GlycA and high-sensitivity C-reactive protein were quantified by nuclear magnetic resonance spectroscopy and immunoturbidimetry, respectively. During median follow-up of 17.2 years, 2087 type 2 diabetes mellitus cases occurred. In Cox models with adjustment for age, race, smoking, alcohol, activity, menopausal status, hormone use, family history, and body mass index, quartile 4 versus 1 hazard ratios and 95% confidence intervals were 2.67 (2.26–3.14) for GlycA and 3.93 (3.24–4.77) for high-sensitivity C-reactive protein; both P trend <0.0001. Associations for GlycA and high-sensitivity C-reactive protein were attenuated after additionally adjusting for lipids: 1.65 (1.39–1.95) and 2.83 (2.32–3.44), respectively, both P trend <0.0001, and after mutual adjustment: 1.11 (0.93–1.33; P trend=0.10) and 2.57 (2.09–3.16; P trend<0.0001), respectively. Conclusions— Our finding of an association between a consensus glycan sequence common to a host of acute-phase reactants and incident type 2 diabetes mellitus provides further support for inflammation in the development of type 2 diabetes mellitus. Additional studies exploring the role of enzymatic glycosylation in the prevention of type 2 diabetes mellitus are warranted. Clinical Trial Registration— URL: . Unique identifier: [NCT00000479][1]. # Significance {#article-title-25} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00000479&atom=%2Fatvbaha%2F35%2F6%2F1544.atom

  • a novel protein glycan biomarker and future cardiovascular disease events
    Journal of the American Heart Association, 2014
    Co-Authors: Akintunde O Akinkuolie, Paul M Ridker, Julie E Buring, Samia Mora
    Abstract:

    Background Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N -acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high-sensitivity C-reactive protein (hsCRP). Methods and Results In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow-up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r =0.61, P <0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both P trend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; P trend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; P trend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; P trend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; P trend=0.001). Conclusions In this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD. Clinical Trial Registration URL: http//clinicaltrials.gov/. Unique identifier [NCT00000479][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00000479&atom=%2Fahaoa%2F3%2F5%2Fe001221.atom

Akintunde O Akinkuolie - One of the best experts on this subject based on the ideXlab platform.

  • circulating n linked glycoprotein side chain biomarker rosuvastatin therapy and incident cardiovascular disease an analysis from the jupiter trial
    Journal of the American Heart Association, 2016
    Co-Authors: Akintunde O Akinkuolie, Robe J Gly, Latha Padmanabha, Paul M Ridke, Samia Mora
    Abstract:

    Background GlycA, a novel protein glycan biomarker of N ‐acetyl side chains of acute‐phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. Methods and Results In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low‐density lipoprotein cholesterol 0.20). Conclusion In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. Clinical Trials Registration URL: . Unique identifier: NCT00239681.

  • circulating n linked glycoprotein side chain biomarker rosuvastatin therapy and incident cardiovascular disease an analysis from the jupiter trial
    Journal of the American Heart Association, 2016
    Co-Authors: Akintunde O Akinkuolie, Robert J Glynn, Latha Padmanabhan, Paul M Ridker, Samia Mora
    Abstract:

    Background GlycA, a novel protein glycan biomarker of N ‐acetyl side chains of acute‐phase proteins, was recently associated with incident cardiovascular disease (CVD) in healthy women. Whether GlycA predicts CVD events in the setting of statin therapy in men and women without CVD but with evidence of chronic inflammation is unknown. Methods and Results In the Justfication for the Use of Statins in Prevention: an Intervention Trial Evaluating Rosuvastatin (JUPITER) trial (NCT00239681), participants with low‐density lipoprotein cholesterol 0.20). Conclusion In the JUPITER trial, increased levels of GlycA were associated with an increased risk of CVD events independent of traditional risk factors and hsCRP. Clinical Trials Registration URL: . Unique identifier: NCT00239681.

  • novel protein glycan side chain biomarker and risk of incident type 2 diabetes mellitus
    Arteriosclerosis Thrombosis and Vascular Biology, 2015
    Co-Authors: Akintunde O Akinkuolie, Paul M Ridker, Julie E Buring, Aruna D Pradhan, Samia Mora
    Abstract:

    Objectives— Enzymatically glycosylated proteins partake in multiple biological processes, including glucose transport and inflammation. We hypothesized that a novel biomarker (GlycA) of N -acetyl methyl groups originating mainly from N -acetylglucosamine moieties of acute-phase glycoproteins is related to incident type 2 diabetes mellitus and compared it with high-sensitivity C-reactive protein. Approach and Results— In 26 508 initially healthy women free of diabetes mellitus, baseline GlycA and high-sensitivity C-reactive protein were quantified by nuclear magnetic resonance spectroscopy and immunoturbidimetry, respectively. During median follow-up of 17.2 years, 2087 type 2 diabetes mellitus cases occurred. In Cox models with adjustment for age, race, smoking, alcohol, activity, menopausal status, hormone use, family history, and body mass index, quartile 4 versus 1 hazard ratios and 95% confidence intervals were 2.67 (2.26–3.14) for GlycA and 3.93 (3.24–4.77) for high-sensitivity C-reactive protein; both P trend <0.0001. Associations for GlycA and high-sensitivity C-reactive protein were attenuated after additionally adjusting for lipids: 1.65 (1.39–1.95) and 2.83 (2.32–3.44), respectively, both P trend <0.0001, and after mutual adjustment: 1.11 (0.93–1.33; P trend=0.10) and 2.57 (2.09–3.16; P trend<0.0001), respectively. Conclusions— Our finding of an association between a consensus glycan sequence common to a host of acute-phase reactants and incident type 2 diabetes mellitus provides further support for inflammation in the development of type 2 diabetes mellitus. Additional studies exploring the role of enzymatic glycosylation in the prevention of type 2 diabetes mellitus are warranted. Clinical Trial Registration— URL: . Unique identifier: [NCT00000479][1]. # Significance {#article-title-25} [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00000479&atom=%2Fatvbaha%2F35%2F6%2F1544.atom

  • a novel protein glycan biomarker and future cardiovascular disease events
    Journal of the American Heart Association, 2014
    Co-Authors: Akintunde O Akinkuolie, Paul M Ridker, Julie E Buring, Samia Mora
    Abstract:

    Background Glycosylated proteins partake in multiple cellular processes including inflammation. We hypothesized that GlycA, a novel biomarker of protein glycan N -acetyl groups, is related to incident cardiovascular disease (CVD), and we compared it with high-sensitivity C-reactive protein (hsCRP). Methods and Results In 27 491 initially healthy women, baseline GlycA was quantified by nuclear magnetic resonance spectroscopy and hsCRP by an immunoturbidimetric assay. During median follow-up of 17.2 years, 1648 incident CVD events occurred (myocardial infarction, ischemic stroke, coronary revascularization, and CVD death). GlycA and hsCRP were moderately correlated (Spearman r =0.61, P <0.0001). In Cox regression models that included age, ethnicity, smoking, blood pressure, medications, menopausal status, body mass index, and diabetes, hazard ratios for CVD across quartiles 1 to 4 of GlycA were 1.00, 1.10 (95% CI, 0.92 to 1.30), 1.34 (95% CI, 1.13 to 1.58), and 1.64 (95% CI, 1.39 to 1.93), similar to hsCRP, for which hazard ratios were 1.00, 1.18 (95% CI, 0.99 to 1.41), 1.35 (95% CI, 1.14 to 1.61), and 1.75 (95% CI, 1.47 to 2.09) (both P trend<0.0001). Associations were attenuated after additionally adjusting for lipids: the hazard ratio of quartile 4 versus 1 for GlycA was 1.23 (95% CI, 1.04 to 1.46; P trend=0.002) and for hsCRP was 1.44 (95% CI, 1.20 to 1.72; P trend<0.0001). Further adjustment for the other biomarker resulted in a hazard ratio of quartile 4 versus 1 for GlycA of 1.03 (95% CI, 0.85 to 1.24; P trend=0.41) and for hsCRP of 1.29 (95% CI, 1.06 to 1.56; P trend=0.001). Conclusions In this prospective study of initially healthy women, baseline GlycA was associated with incident CVD, consistent with a possible role for protein glycans in inflammation and CVD. Clinical Trial Registration URL: http//clinicaltrials.gov/. Unique identifier [NCT00000479][1]. [1]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT00000479&atom=%2Fahaoa%2F3%2F5%2Fe001221.atom

Jolanda Spadavecchia - One of the best experts on this subject based on the ideXlab platform.

  • lactose modified chitosan gold iii pegylated complex bioconjugates from synthesis to interaction with targeted galectin 1 protein
    Bioconjugate Chemistry, 2018
    Co-Authors: Qiqian Liu, Pasquale Sacco, Eleonora Marsich, Franco Furlani, Celia Arib, Nadia Djaker, Marc Lamy De La Chapelle, Ivan Donati, Jolanda Spadavecchia
    Abstract:

    Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV–vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10–12 M). We observed that the interaction was strong...

  • Lactose-Modified Chitosan Gold(III)-PEGylated Complex-Bioconjugates: From Synthesis to Interaction with Targeted Galectin‑1 Protein
    2018
    Co-Authors: Qiqian Liu, Pasquale Sacco, Eleonora Marsich, Franco Furlani, Celia Arib, Nadia Djaker, Marc Lamy De La Chapelle, Ivan Donati, Jolanda Spadavecchia
    Abstract:

    Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV–vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10–12 M). We observed that the interaction was strongly dependent on the Gal-1 concentration at the surface of the gold nanoparticles

Marc Lamy De La Chapelle - One of the best experts on this subject based on the ideXlab platform.

  • lactose modified chitosan gold iii pegylated complex bioconjugates from synthesis to interaction with targeted galectin 1 protein
    Bioconjugate Chemistry, 2018
    Co-Authors: Qiqian Liu, Pasquale Sacco, Eleonora Marsich, Franco Furlani, Celia Arib, Nadia Djaker, Marc Lamy De La Chapelle, Ivan Donati, Jolanda Spadavecchia
    Abstract:

    Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV–vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10–12 M). We observed that the interaction was strong...

  • Lactose-Modified Chitosan Gold(III)-PEGylated Complex-Bioconjugates: From Synthesis to Interaction with Targeted Galectin‑1 Protein
    2018
    Co-Authors: Qiqian Liu, Pasquale Sacco, Eleonora Marsich, Franco Furlani, Celia Arib, Nadia Djaker, Marc Lamy De La Chapelle, Ivan Donati, Jolanda Spadavecchia
    Abstract:

    Galectins (Gal) are a family of glycan-binding proteins characterized by their affinity for β-galactosides. Galectin-1 (Gal-1), a dimeric lectin with two galactoside-binding sites, regulates cancer progression and immune responses. Coordination chemistry has been engaged to develop versatile multivalent neoglycoconjugates for binding Gal-1. In this study we report a fast and original method to synthesize hybrid gold nanoparticles in which a hydrochloride lactose-modified chitosan, named CTL, is mixed with dicarboxylic acid-terminated polyethylene glycol (PEG), leading to shell-like hybrid polymer-sugar-metal nanoparticles (CTL-PEG-AuNPs). The aim of this paper is to preliminarily study the interaction of the CTL-PEG-AuNPs with a target protein, namely, Gal-1, under specific conditions. The molecular interaction has been measured by Transmission Electron Microscopy (TEM), UV–vis, and Raman Spectroscopy on a large range of Gal-1 concentrations (from 0 to 10–12 M). We observed that the interaction was strongly dependent on the Gal-1 concentration at the surface of the gold nanoparticles