22900-11-4Relevant academic research and scientific papers
Quantitative Standards of 4-O-Acetyl- and 9-O-Acetyl-N-Acetylneuraminic Acid for the Analysis of Plasma and Serum
Cheeseman, Jack,Badia, Concepcion,Thomson, Rebecca I.,Kuhnle, Gunter,Gardner, Richard A.,Spencer, Daniel I. R.,Osborn, Helen M. I.
, (2022/01/20)
N-Acetylneuraminic acid (sialic acid, Neu5Ac) is one of a large, diverse family of nine-carbon monosaccharides that play roles in many biological functions such as immune response. Neu5Ac has previously been identified as a potential biomarker for the presence and pathogenesis of cardiovascular disease (CVD), diabetes and cancer. More recent research has highlighted acetylated sialic acid derivatives, specifically Neu5,9Ac2, as biomarkers for oral and breast cancers, but advances in analysis have been hampered due to a lack of commercially available quantitative standards. We report here the synthesis of 9-O- and 4-O-acetylated sialic acids (Neu5,9Ac2 and Neu4,5Ac2) with optimisation of previously reported synthetic routes. Neu5,9Ac2 was synthesised in 1 step in 68 % yield. Neu4,5Ac2 was synthesised in 4 steps in 39 % overall yield. Synthesis was followed by analysis of these standards via quantitative NMR (qNMR) spectroscopy. Their utilisation for the identification and quantification of specific acetylated sialic acid derivatives in biological samples is also demonstrated.
One pot synthesis of thio -glycosides via aziridine opening reactions
Hribernik, Nives,Tamburrini, Alice,Falletta, Ermelinda,Bernardi, Anna
supporting information, p. 233 - 247 (2021/01/14)
A one-pot aziridine opening reaction by glycosyl thiols generated in situ from the corresponding anomeric thio-acetates affords thio-glycosides with a pseudo-disaccharide structure and an N-linked tether. The scope of the one-pot aziridine opening reaction was explored on a series of mono- and disaccharides, creating a class of pseudo-glycosidic compounds with potential for further functionalization. Unexpected anomerization of glycosyl thiols was observed under the reaction conditions and the influence of temperature, base and solvent on the isomerization was investigated. Single isomers were obtained in good to acceptable yields for mannose, rhamnose and sialic acid derivatives. The class of thio-glycomimetics synthesized can potentially be recognized by various lectins, while presenting hydrolytic and enzymatic stability. The nitrogen functionality incorporated in the glycomimetics can be exploited for further functionalization, including tethering to linkers, scaffolds or peptide residues.
Revealing Functional Significance of Interleukin-2 Glycoproteoforms Enabled by Expressed Serine Ligation
Cao, Qi,Li, Bin,Liu, Jiazhi,Liu, Lizhen,Liu, Xinnan,Shao, Hong,Tao, Houchao,Wang, Can,Wang, Ping,Xue, Dongxiang,Ye, Farong,Yu, Biao,Zhao, Hongbo,Zhao, Jie
supporting information, (2022/01/31)
Naturally occurring interleukin-2 (IL-2) is a pleiotropic glycoprotein that regulates immune responses by controlling the differentiation and homeostasis of T cells. Non-glycosylated IL-2 has been used in clinical settings for three decades. However, the function of the O-glycan of native IL-2 remains elusive. Herein, to stress this issue, we report a highly efficient semi-synthesis of homogeneous glycosylated IL-2 with various glycoproteoforms on a multi-milligram scale. The glycopeptide fragment was prepared by chemical synthesis and then merged with recombinant fragment via a serine ligation to generate the desired glycoprotein in a single operation. Biological evaluation of the homogenous glycoprotein library reveals that the activity of IL-2 in activating individual T cell subset is glycan dependent, thus highlighting the possibility of further improving current clinical medicine.
Addition of Sialic Acid to Insulin Confers Superior Physical Properties and Bioequivalence
Kabotso, Daniel E. K.,Kabotso, Daniel E. K.,Smiley, David,Mayer, John P.,Gelfanov, Vasily M.,Perez-Tilve, Diego,Dimarchi, Richard D.,Pohl, Nicola L. B.,Liu, Fa
, p. 6134 - 6143 (2020/07/10)
Native insulin is susceptible to biophysical aggregation and fibril formation, promoted by manual agitation and elevated temperatures. The safety of the drug and its application to alternative forms of administration could be enhanced through the identification of chemical modifications that strengthen its physical stability without compromising its biological properties. Complex polysialic acids (PSAs) exist naturally and provide a means to enhance the physical properties of peptide therapeutics. A set of insulin analogues site-specifically derivatized with sialic acid were prepared in an overall yield of 50-60%. Addition of a single or multiple sialic acids conferred remarkable enhancement to the biophysical stability of human insulin while maintaining its potency. The time to the onset of fibrillation was extended by more than 10-fold relative to that of the native hormone. These results demonstrate that simplified sialic acid conjugates represent a viable alternative to complex natural PSAs in increasing the stability of therapeutic peptides.
MATERIALS AND METHODS FOR THE PREPARATION OF BACTERIAL CAPSULAR POLYSACCHARIDES
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Paragraph 0009; 0097, (2020/08/22)
Methods for preparing saccharide products such as bacterial capsular polysaccharides are provided. The methods include: forming a reaction mixture containing one or more bacterial capsular polysaccharide synthases, a sugar acceptor, and one or more sugar
Synthesis of an STnThr analogue, structurally based on a TnThr antigen mimetic
Papi, Francesco,Paris, Arnaud,Lafite, Pierre,Daniellou, Richard,Nativi, Cristina
supporting information, p. 7366 - 7372 (2020/10/13)
The monosaccharide Tn and the disaccharide STn are tumor antigens with similar structures and common biosynthetic pathways. Both are always over-expressed simultaneously on tumor cell surfaces. We report herein the efficient synthesis of the STnThr antigen analogue 2, featuring the immunogenic TnThr mimetic 1 aglycon. Analogously to the native STn, 2 is recognized by the influenza N1 neuraminidase. A model of the N1·2 complex showed the sialyl moiety of 2 well nested in the active site pocket, with docking unaffected by the rigid aglycon. The analogue 2 is, therefore, in association with mimetic 1, a good determinant for the design of new multiantigen cancer vaccines.
Cooperative Multipoint Recognition of Sialic Acid by Benzoboroxole-Based Receptors Bearing Cationic Hydrogen-Bond Donors
Di Pasquale, Alice,Tommasone, Stefano,Xu, Lili,Ma, Jing,Mendes, Paula M.
, p. 8330 - 8338 (2020/07/17)
Sialic acid recognition remains an interesting and challenging target in molecular receptor design. Herein, we report a series of benzoboroxole-based receptors in which cationic hydrogen-bond donors have been introduced and shown to promote multipoint sialic acid recognition. One striking feature revealed by these receptors is that the carboxylate sialic acid residue is the primary binding determinant for recognition by benzoboroxole, in which the presence of charge-reinforced hydrogen bonds results in enhanced selectivity for sialic acid over other carbohydrates and a 4.5-fold increase in affinity. These findings open up wide possibilities for benzoboroxole-based receptors use in life science research, biotechnology, and diagnostics.
SMALL MOLECULE LIGAND-TARGETED DRUG CONJUGATES FOR ANTI-INFLUENZA CHEMOTHERAPY AND IMMUNOTHERAPY
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Page/Page column 20, (2020/02/16)
Disclosed herein is a small molecule targeted drug conjugate for anti-influenza chemotherapy and immunotherapy. The disclosed drug conjugate may form an adaptor to recruit additional CAR T cells or other immune cells for precise elimination of influenza virus-infected cells in a subject. Concurrently administered antibodies or pre-existing immunity in influenza-virus infected subject works well with the targeted conjugate to eliminate virus infected cells, saving valuable time for rescuing late stage patients.
A glycal-based photoaffinity probe that enriches sialic acid binding proteins
Thuy-Boun, Peter S.,Wolan, Dennis W.
supporting information, p. 2609 - 2612 (2019/08/07)
To identify sialic acid binding proteins from complex proteomes, three photocrosslinking affinity-based probes were constructed using Neu5Ac (5 and 6) and Neu5Ac2en (7) scaffolds. Kinetic inhibition assays and Western blotting revealed the Neu5Ac2en-based 7 to be an effective probe for the labeling of a purified gut microbial sialidase (BDI_2946) and a purified human sialic acid binding protein (hCD33). Additionally, LC–MS/MS affinity-based protein profiling verified the ability of 7 to enrich a low-abundance sialic acid binding protein (complement factor H) from human serum thus validating the utility of this probe in a complex context.
Glycopeptide nanofiber platform for Aβ-sialic acid interaction analysis and highly sensitive detection of Aβ
Lei, Li,Geng, Rui,Xu, Zhiai,Dang, Yijing,Hu, Xianli,Li, Lingling,Geng, Ping,Tian, Yang,Zhang, Wen
, p. 8129 - 8136 (2019/08/26)
The variation of amyloid β peptide (Aβ) concentration and Aβ aggregation are closely associated with the etiology of Alzheimer’s diseases (AD). The interaction of Aβ with the monosialoganglioside-rich neuronal cell membrane has been suggested to influence Aβ aggregation. Therefore, studies on the mechanism of Aβ and sialic acids (SA) interaction would greatly contribute to better understanding the pathogenesis of AD. Herein, we report a novel approach for Aβ?SA interaction analysis and highly sensitive Aβ detection by mimicing the cell surface presentation of SA clusters through engineering of SA-modified peptide nanofiber (SANF). The SANF displayed well-ordered 1D nanostructure with high density of SA on surface. Using FAM-labeled Aβ fragments of Aβ1?16, Aβ16?23, and Aβ24?40, the interaction between Aβ and SA was evaluated by the fluorescence titration experiments. It was found that the order of the SA-binding affinity was Aβ1?16 > Aβ24?40 > Aβ16?23. Importantly, the presence of full-length Aβ1?40 monomer triggered a significant fluorescence enhancement due to the multivalent binding of Aβ1?40 to the nanofiber. This fluorescent turn-on response showed high selectivity and sensitivity for Aβ1?40 detection and the method was further used for Aβ aggregation process monitoring and inhibitor screening. The results suggest the proposed strategy is promising to serve as a tool for mechanism study and the early diagnosis of Alzheimer’s disease.
