653600-56-7Relevant academic research and scientific papers
Nanobody-Engineered Natural Killer Cell Conjugates for Solid Tumor Adoptive Immunotherapy
Chen, Ying,Cui, Kaisa,Gong, Liang,Hong, Haofei,Huang, Zhaohui,Li, Dan,Li, Jiuming,Li, Yanchun,Wu, Zhimeng,Yin, Yuan
, (2021/11/16)
Cancer immunotherapy based on natural killer (NK) cells is demonstrated to be a promising strategy. However, NK cells are deficient in ligands that target specific tumors, resulting in limited antitumor efficacy. Here, a glycoengineering approach to imitate the chimeric antigen receptor strategy and decorate NK cells with nanobodies to promote NK-based immunotherapy in solid tumors is proposed. Nanobody 7D12, which specifically recognizes the human epidermal growth factor receptor (EGFR) that is overexpressed on many solid tumors, is coupled to the chemically synthesized DBCO-PEG4-GGG-NH2 by sortase A-mediated ligation to generate DBCO-7D12. The NK92MI cells bearing azide groups are then equipped with DBCO-7D12 via bioorthogonal click chemistry. The resultant 7D12-NK92MI cells exhibit high specificity and affinity for EGFR-overexpressing tumor cells in vitro and in vivo by the 7D12-EGFR interaction, causing increased cytokine secretion to more effectively kill EGFR-positive tumor cells, but not EGFR-negative cancer cells. Importantly, the 7D12-NK92MI cells also show a wide anticancer spectrum and extensive tumor penetration. Furthermore, mouse experiments reveal that 7D12-NK92MI treatment achieves excellent therapeutic efficacy and outstanding safety. The authors’ works provide a cell modification strategy using specific protein ligands without genetic manipulation and present a potential novel method for cancer-targeted immunotherapy by NK cells.
Selective Engineering of Linkage-Specific α2,6-N-Linked Sialoproteins Using Sydnone-Modified Sialic Acid Bioorthogonal Reporters
Chinoy, Zoeisha S.,Bodineau, Clément,Favre, Camille,Moremen, Kelley W.,Durán, Raúl V.,Friscourt, Frédéric
supporting information, p. 4281 - 4285 (2019/02/28)
The metabolic oligosaccharide engineering (MOE) strategy using unnatural sialic acids has recently enabled the visualization of the sialome in living systems. However, MOE only reports on global sialylation and dissected information regarding subsets of s
The Bioorthogonal Isonitrile-Chlorooxime Ligation
Li, Mao,Monaco, Mattia R.,Rivera-Fuentes, Pablo,Sch?fer, Rebecca J. B.,Tirla, Alina,Wennemers, Helma
supporting information, p. 18644 - 18648 (2019/11/28)
Bioorthogonal reactions are valuable tools for the selective labeling and imaging of natural products and proteins. Here, we present the reaction between isonitriles and chlorooximes as a ligation that proceeds quickly (k ≈ 1 M-1 s-1
Novel Liposomal Azido Mannosamine Lipids on Metabolic Cell Labeling and Imaging via Cu-Free Click Chemistry
Shen, Li,Cai, Kaimin,Yu, Jin,Cheng, Jianjun
, p. 2317 - 2322 (2019/09/06)
In comparison with the popular Ac4ManNAz applied as cell labels via Cu-free click chemistry, two novel azido mannosamine lipids with C6 and C12 esters on anomeric hydroxyl groups were prepared and encapsulated in a liposome delivery system, which enhanced chemical stabilities and showed good cell-metabolizable labeling efficiency on MDA-MB-231 cells with strong fluorescence after the treatment of DBCO-Cy5 by triazole formation via click chemistry.
Direct One-Step Fluorescent Labeling of O-GlcNAc-Modified Proteins in Live Cells Using Metabolic Intermediates
Tan, Hong Yee,Eskandari, Razieh,Shen, David,Zhu, Yanping,Liu, Ta-Wei,Willems, Lianne I.,Alteen, Matthew G.,Madden, Zarina,Vocadlo, David J.
supporting information, p. 15300 - 15308 (2018/11/03)
The modification of proteins with O-linked N-acetylglucosamine (O-GlcNAc) by the enzyme O-GlcNAc transferase (OGT) has emerged as an important regulator of cellular physiology. Metabolic labeling strategies to monitor O-GlcNAcylation in cells have proven of great value for uncovering the molecular roles of O-GlcNAc. These strategies rely on two-step labeling procedures, which limits the scope of experiments that can be performed. Here, we report on the creation of fluorescent uridine 5′-diphospho-N-acetylglucosamine (UDP-GlcNAc) analogues in which the N-acyl group of glucosamine is modified with a suitable linker and fluorophore. Using human OGT, we show these donor sugar substrates permit direct monitoring of OGT activity on protein substrates in vitro. We show that feeding cells with a corresponding fluorescent metabolic precursor for the last step of the hexosamine biosynthetic pathway (HBP) leads to its metabolic assimilation and labeling of O-GlcNAcylated proteins within live cells. This one-step metabolic feeding strategy permits labeling of O-GlcNAcylated proteins with a fluorescent glucosamine-nitrobenzoxadiazole (GlcN-NBD) conjugate that accumulates in a time- and dose-dependent manner. Because no genetic engineering of cells is required, we anticipate this strategy should be generally amenable to studying the roles of O-GlcNAc in cellular physiology as well as to gain an improved understanding of the regulation of OGT within cells. The further expansion of this one-step in-cell labeling strategy should enable performing a range of experiments including two-color pulse chase experiments and monitoring OGT activity on specific protein substrates in live cells.
Synthesis of a novel fluorescent ruthenium complex with an appended Ac4GlcNAc moiety by click reaction
Cheng, Qi,Cui, Yalu,Xiao, Nao,Lu, Jishun,Fang, Chen-Jie
, p. 1 - 10 (2018/07/31)
The O-linked β-N-acetylglucosamine (O-GlcNAc) modification is an abundant post-translational modification in eukaryotic cells, which plays a fundamental role in the activity of many cells and is associated with pathologies like type II diabetes, Alzheimer’s disease or some cancers. However, the precise connexion between O-GlcNAc-modified proteins and their function in cells is largely undefined for most cases. Confocal microscopy is a powerful and effective tool for in-cell elucidation of the function of biological molecules. Chemical labeling of non-ultraviolet or non-fluorescent carbohydrates with fluorescent tag is an essential step that makes intra-cellular microscopic inspection possible. Here we report a strategy based on the 1,3-dipolar cycloaddition, called click chemistry, between unnatural N-acetylglucosamine (GlcNAc) analogues Ac4GlcNAc (substituted with an azido group) and the corresponding fluorescent tag Ru(bpy)2(Phen-alkyne)Cl2 (4) to synthesize the fluorescent dye Ru(bpy)2(Phen-Ac4GlcNAc)Cl2 (5) under mild and neutral reaction conditions. Moreover, 5 showed good stability, desirable fluorescence characteristics, and exhibited rather low levels of cytotoxicity against sensitive MCF-7 cells. Additionally, we have achieved successful fluorescent imaging of 5 transported in living MCF-7 cells. Cell images displayed that proteins are potentially labelled with 5 in the cytoplasm.
TRIGGER-ACTIVATABLE SUGAR CONJUGATES FOR CANCER-SELECTIVE LABELING AND TARGETING
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Page/Page column 69; 70, (2018/09/08)
Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl-drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity. Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds.
Design, synthesis and cytotoxic activity of N-Modified oleanolic saponins bearing A glucosamine
Lin, You-Yu,Chan, She-Hung,Juang, Yu-Pu,Hsiao, Hsin-Min,Guh, Jih-Hwa,Liang, Pi-Hui
supporting information, p. 1942 - 1958 (2017/11/16)
A series of N-acyl, N-alkoxycarbonyl, and N-alkylcarbamoyl derivatives of 2′-deoxy-glucosyl bearing oleanolic saponins were synthesized and evaluated against HL-60, PC-3, and HT29 tumor cancer cells. The SAR studies revealed that the activity increased in order of conjugation of 2′ -amino group with carbamate > amide > urea derivatives. Lengthening the alkyl chain increased the cytotoxicity, the peak activity was found to around heptyl to nonyl substitutions. 2′-N-heptoxycarbonyl derivative 56 was found to be the most cytotoxic (IC50 = 0.76 μM) against HL-60 cells. Due to the interesting SARs of alkyl substitutions, we hypothesized that their location in the cell was different, and pursued a location study using 2′-(4″-pentynoylamino) 2′-deoxy-glucosyl OA, which suggested that these compounds distributed mainly in the cytosol.
TRIGGER-ACTIVATABLE METABOLIC SUGAR PRECURSORS FOR CANCER-SELECTIVE LABELING AND TARGETING
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Page/Page column 51; 52, (2017/08/01)
Disclosed are compounds for the selective labeling of cell-surface sugars in cancer cells. The compounds are activatable by triggers specific to cancer cells, and, when metabolized, label a cancer cell surface sugar with an azide chemical group. Facilitated by a click chemistry reaction, combination of the cell surface-expressed azide with a alkynyl- drug conjugate enables efficient targeted drug delivery to cancer cells with reduced toxicity Also disclosed are compounds for delivering a drug to an azide-bearing cancer cell, and methods of treating cancer using the compounds of the invention.
The synthesis of new fluorinated or nonfluorinated sugar phosphonates and phosphoramidates as building blocks in the synthesis of modified hyaluronic acid subunits
Koroniak-Szejn, Katarzyna,Tomaszewska, Joanna,Koroniak, Henryk
, p. 683 - 694 (2017/06/05)
The synthesis of several new fluorinated or nonfluorinated sugar phosphonates and phosphoramidates as building blocks for the synthesis of modified hyaluronic acid subunits is described. These compounds were prepared from d-glucose and d-glucosamine hydro
