Tools for Precise Control of Protein-Specific O-GlcNAcylation: Insights into Disease Mechanisms and Therapeutic Opportunities

doi:10.6023/A25120390

Acta Chimica Sinica ›› 2026, Vol. 84 ›› Issue (3): 409-424.DOI: 10.6023/A25120390 Previous Articles Next Articles

Review

靶向特定蛋白质的O-GlcNAc修饰精准调控工具:疾病机制研究与治疗机遇

于恺然^a, 张娜娜^b, 刘宇博^b^,^*()

^a 大连理工大学化工海洋与生命学院盘锦 122406
^b 东北大学生命科学与健康学院沈阳 110169

投稿日期:2025-12-01 发布日期:2026-02-10

作者简介:

于恺然, 大连理工大学化学生物学专业在读博士生, 研究方向为O-GlcNAc糖基化修饰与肿瘤生物学行为.

刘宇博, 博士, 教授, 博士生导师. 现就职于东北大学生命科学与健康学院. 研究工作以化学生物学与糖生物学交叉融合为手段, 通过开发高效、低毒糖探针与化学糖组学新策略, 实现对肿瘤演进过程的多维度、高通量观测; 开发人源化糖链生物合成方法, 构建以糖基转移酶、糖核苷酸合成与转运模块为核心的可编程平台. 在Nature Communications、Science Advances、Oncogene、EMBO Reports等杂志发表论文50余篇. 主持国家自然科学基金, 国家重大科技专项子课题等十余项, 入选国家级青年人才, “兴辽英才”青年拔尖人才.

基金资助:
项目受国家自然科学基金(32471331)

Tools for Precise Control of Protein-Specific O-GlcNAcylation: Insights into Disease Mechanisms and Therapeutic Opportunities

Yu Kairan^a, Zhang Nana^b, Liu Yubo^b^,^*()

^a School of Chemical Engineering, Ocean and Life Sciences, Dalian University of Technology, Panjin 122406, China
^b School of Life Sciences and Health, Northeastern University, Shenyang 110169, China

Received:2025-12-01 Published:2026-02-10
Contact: *E-mail: liuyubo@mail.neu.edu.cn
Supported by:
National Natural Science Foundation of China(32471331)

Protein O-linked β-N-acetylglucosamine (O-GlcNAc) glycosylation is a highly dynamic and reversible monosaccharide post-translational modification in eukaryotic cells, playing critical roles in cellular regulation. To date, more than 5,000 O-GlcNAc-modified proteins have been identified, distributed in the cytoplasm, nucleus, mitochondria, and membraneless subcellular compartments. O-GlcNAcylation is catalyzed by O-GlcNAc transferase (OGT), which installs a single N-acetylglucosamine moiety onto serine and threonine residues, whereas removal of the modification is mediated by O-GlcNAcase (OGA). Uridine diphosphate N-acetylglucosamine (UDP-GlcNAc), the end product of the hexosamine biosynthetic pathway (HBP), serves as the sugar donor for this modification. This tightly coupled enzymatic cycle allows O-GlcNAcylation to act as a nutrient- and signal-responsive regulatory modification, linking metabolic state to protein function. O-GlcNAcylation regulates a broad range of fundamental cellular processes, including gene transcription, chromatin remodeling, epigenetic regulation, protein-protein interactions, and diverse intracellular signaling pathways. Dysregulation of global or protein-specific O-GlcNAcylation has been linked to the development and progression of multiple human diseases, including cancer, diabetes, and neurodegenerative disorders. With continuous advances in analytical methodologies, particularly high-resolution mass spectrometry and enrichment strategies, an increasing number of O-GlcNAc modification sites have been identified, allowing the functional roles of target proteins and their specific modification sites to be examined in detail. However, the highly dynamic nature of O-GlcNAcylation implies that chemical or genetic methods targeting OGT or OGA often lead to widespread changes in O-GlcNAc levels across thousands of proteins. Such global alterations complicate the functional interpretation of site-specific modifications and make it challenging to determine the precise role of O-GlcNAc at individual protein sites. Increasing evidence suggests that targeted modulation of specific O-GlcNAc sites on individual proteins provides improved mechanistic insight and greater translational relevance than global modulation approaches. Therefore, developing tools and strategies that allow site-specific modulation of O-GlcNAcylation on individual proteins, without altering overall O-GlcNAc levels, is critical. This review summarizes recent advances in targeted protein O-GlcNAcylation, highlights emerging chemical biology tools and strategies, and discusses their potential to reveal site-specific O-GlcNAc functions and their relevance to human disease.

Key words: O-GlcNAcylation, chemical biology, molecular tools, targeted regulation, site-specific modification

Cite this article

Yu Kairan, Zhang Nana, Liu Yubo. Tools for Precise Control of Protein-Specific O-GlcNAcylation: Insights into Disease Mechanisms and Therapeutic Opportunities[J]. Acta Chimica Sinica, 2026, 84(3): 409-424.

Export EndNote|Reference Manager|ProCite|BibTeX|RefWorks

share this article

Fig. & Tab. 10

Figure 1. The O-GlcNAcylation modification process

Figure 2. Chemical and labeling approaches for investigating O-GlcNAc modifications

Figure 3. Loss-of-function O-GlcNAc site mutations

Figure 4. The S-GlcNAcylation modification process

Figure 5. Gain-of-function O-GlcNAc site mutations

Figure 6. Process of genetic code expansion

Figure 7. Process of the GECCO strategy

Figure 8. Nanobody-based targeted regulation of O-GlcNAcylation. (a) OGT is recruited into proximity of the target protein via a tag-specific nanobody, leading to increased O-GlcNAcylation on the tagged target protein. (b) OGA removes O-GlcNAc from the target protein via the tag-specific nanobody. Splitting the OGA stalk and catalytic domains can suppress off-target activity

Figure 9. Chimeric molecules for targeting O-GlcNAcylation to specific proteins. (a) OGT fused to FKBP12F36V is recruited to HaloTag-fused target proteins via OGTAC-1/2/3, resulting in O-GlcNAcylation of the target proteins. (b) OGT fused to FKBP12F36V directly binds the endogenous protein BRD4 through OGTAC-4, leading to O-GlcNAcylation of BRD4

Figure 10. Dual-specificity RNA aptamers

References 144

[46]	Ma B.; Khan K. S.; Xu T.; Xeque Amada J.; Guo Z.; Huang Y.; Yan Y.; Lam H.; Cheng A. S.-L.; Ng B. W.-L. J. Am. Chem. Soc. 2024, 146, 9779. doi: 10.1021/jacs.3c14380
[47]	Xu T.; Ma B.; Li Y.; Guo Z.; Zhang M.; Ng B. W.-L. ACS Chem. Biol. 2025, 20, 1646. doi: 10.1021/acschembio.5c00223
[48]	Zhu Y.; Hart G. W. Cell 2023, 186, 428. doi: 10.1016/j.cell.2022.12.016 pmid: 36626902
[49]	Gold L.; Janjic N.; Jarvis T.; Schneider D.; Walker J. J.; Wilcox S. K.; Zichi D. Cold Spring Harb. Perspect. Biol. 2012, 4, a003582.
[50]	Lazarus M. B.; Nam Y.; Jiang J.; Sliz P.; Walker S. Nature 2011, 469, 564. doi: 10.1038/nature09638
[51]	Jung H.-Y.; Jun S.; Lee M.; Kim H.-C.; Wang X.; Ji H.; McCrea P. D.; Park J.-I. Mol. Cell 2013, 52, 193. doi: 10.1016/j.molcel.2013.08.028
[52]	Lévy L.; Wei Y.; Labalette C.; Wu Y.; Renard C.-A.; Buendia M. A.; Neuveut C. Mol. Cell. Biol. 2004, 24, 3404. doi: 10.1128/MCB.24.8.3404-3414.2004
[1]	Kreppel L. K.; Hart G. W. J. Biol. Chem. 1999, 274, 32015. doi: 10.1074/jbc.274.45.32015 pmid: 10542233
[2]	Holt G. D.; Hart G. W. J. Biol. Chem. 1986, 261, 8049. pmid: 3086323
[3]	Hu Y.; Suarez J.; Fricovsky E.; Wang H.; Scott B. T.; Trauger S. A.; Han W.; Hu Y.; Oyeleye M. O.; Dillmann W. H. J. Biol. Chem. 2009, 284, 547. doi: 10.1074/jbc.M808518200
[4]	Love D. C.; Kochran J.; Cathey R. L.; Shin S.-H.; Hanover J. A. J. Cell Sci. 2003, 116, 647. doi: 10.1242/jcs.00246
[5]	Issad T.; Al-Mukh H.; Bouaboud A.; Pagesy P. J. Biomed. Sci. 2022, 29, 64. doi: 10.1186/s12929-022-00851-w
[6]	Fang D.; Zhang X.-L. Chin. J. Biochem. Mol. Biol. 2024, 4, 484 (in Chinese).
	(方丹, 章晓联, 中国生物化学与分子生物学报, 2024, 4, 484.)
[7]	Slawson C.; Hart G. W. Nat. Rev. Cancer 2011, 11, 678. doi: 10.1038/nrc3114 pmid: 21850036
[8]	Masaki N.; Feng B.; Bretón‐Romero R.; Inagaki E.; Weisbrod R. M.; Fetterman J. L.; Hamburg N. M. J. Am. Heart Assoc. 2020, 9, e014046.
[9]	Zhang D.; Qi Y.; Inuzuka H.; Liu J.; Wei W. J. Biol. Chem. 2024, 300, 107709. doi: 10.1016/j.jbc.2024.107709
[10]	Sun K.; Zhi Y.; Ren W.; Li S.; Zheng J.; Gao L.; Zhi K. Exp. Hematol. Oncol. 2024, 13, 107. doi: 10.1186/s40164-024-00569-5
[11]	Wang J.; Xie Y.; Liu L.; Rong S.; Cai H.; Zeng H.; Zhou L.; Deng K.; Dai M.; Xu C.; Zhu Y.; Lu Z.; Song X.; Zeng X.; Liu S. J. Immunother. Cancer 2025, 13, e011479.
[12]	Du P.; Zhang X.; Lian X.; Hölscher C.; Xue G. J. Alzheimer's Dis. 2024, 97, 1051.
[13]	Alghusen I. M.; Carman M. S.; Wilkins H. M.; Strope T. A.; Gimore C.; Fedosyuk H.; Shawa J.; Ephrame S. J.; Denson A. R.; Wang X.; Swerdlow R. H.; Slawson C. Front. Aging Neurosci. 2024, 16, 1387931. doi: 10.3389/fnagi.2024.1387931
[53]	Sherlock M. E.; Breaker R. R. RNA 2020, 26, 675. doi: 10.1261/rna.074997.120
[54]	Mandal M.; Breaker R. R. Nat. Rev. Mol. Cell Biol. 2004, 5, 451. doi: 10.1038/nrm1403
[55]	Dolgosheina E. V.; Jeng S. C.; Panchapakesan S. S. S.; Cojocaru R.; Chen P. S.; Wilson P. D.; Hawkins N.; Wiggins P. A.; Unrau P. J. ACS Chem. Biol. 2014, 9, 2412. doi: 10.1021/cb500499x pmid: 25101481
[56]	Meinjohanns E.; Meldal M.; Bock K. Tetrahedron Lett. 1995, 36, 9205. doi: 10.1016/0040-4039(95)01941-A
[57]	De Leon C. A.; Lang G.; Saavedra M. I.; Pratt M. R. Org. Lett. 2018, 20, 5032. doi: 10.1021/acs.orglett.8b02182
[58]	Dawson P. E.; Muir T. W.; Clark-Lewis I.; Kent S. B. Science 1994, 266, 776. doi: 10.1126/science.7973629 pmid: 7973629
[59]	Mueller L. K.; Baumruck A. C.; Zhdanova H.; Tietze A. A. Front. Bioeng. Biotechnol. 2020, 8, 162. doi: 10.3389/fbioe.2020.00162 pmid: 32195241
[60]	Muir T. W.; Sondhi D.; Cole P. A. Proc. Natl. Acad. Sci. U. S. A. 1998, 95, 6705. doi: 10.1073/pnas.95.12.6705
[61]	Shi J.; Tomašič T.; Sharif S.; Brouwer A. J.; Anderluh M.; Ruijtenbeek R.; Pieters R. J. FEBS Lett. 2017, 591, 1872. doi: 10.1002/feb2.2017.591.issue-13
[14]	Gamage K.; Wang B.; Hard E. R.; Van T.; Galesic A.; Phillips G. R.; Pratt M.; Lapidus L. J. ACS Chem. Neurosci. 2024, 15, 3044. doi: 10.1021/acschemneuro.4c00301 pmid: 39082221
[15]	Zhang N.-N.; Yu K.-R.; Li J.-T.; Zhang J.-N.; Liu Y.-B. Acta Chim. Sinica 2023, 81, 843 (in Chinese). doi: 10.6023/A23020040
	(张娜娜, 于恺然, 李际婷, 张嘉宁, 刘宇博, 化学学报, 2023, 81, 843.) doi: 10.6023/A23020040
[16]	Boyce M.; Carrico I. S.; Ganguli A. S.; Yu S.-H.; Hangauer M. J.; Hubbard S. C.; Kohler J. J.; Bertozzi C. R. PNAS 2011, 108, 3141. doi: 10.1073/pnas.1010045108
[17]	Khidekel N.; Arndt S.; Lamarre-Vincent N.; Lippert A.; Poulin-Kerstien K. G.; Ramakrishnan B.; Qasba P. K.; Hsieh-Wilson L. C. J. Am. Chem. Soc. 2003, 125, 16162. pmid: 14692737
[18]	Griffin M. E.; Jensen E. H.; Mason D. E.; Jenkins C. L.; Stone S. E.; Peters E. C.; Hsieh-Wilson L. C. Mol. Biosyst. 2016, 12, 1756. doi: 10.1039/C6MB00138F
[19]	Wen L.; Zheng Y.; Jiang K.; Zhang M.; Kondengaden S. M.; Li S.; Huang K.; Li J.; Song J.; Wang P. G. J. Am. Chem. Soc. 2016, 138, 11473. doi: 10.1021/jacs.6b07132
[62]	Sharif S.; Shi J.; Ruijtenbeek R.; Pieters R. J. Amino Acids 2019, 51, 739. doi: 10.1007/s00726-019-02699-1
[63]	Tarrant M. K.; Rho H.-S.; Xie Z.; Jiang Y. L.; Gross C.; Culhane J. C.; Yan G.; Qian J.; Ichikawa Y.; Matsuoka T.; Zachara N.; Etzkorn F. A.; Hart G. W.; Jeong J. S.; Blackshaw S.; Zhu H.; Cole P. A. Nat. Chem. Biol. 2012, 8, 262. doi: 10.1038/nchembio.771
[64]	Schwagerus S.; Reimann O.; Despres C.; Smet‐Nocca C.; Hackenberger C. P. J. Pept. Sci. 2016, 22, 327. doi: 10.1002/psc.2870 pmid: 27071766
[65]	Sun Z.; Liu H.; Li X. Chem 2024, 10, 767. doi: 10.1016/j.chempr.2023.10.020
[66]	Chalker J. M.; Bernardes G. J.; Davis B. G. Acc. Chem. Res. 2011, 44, 730. doi: 10.1021/ar200056q
[67]	Raj R.; Lercher L.; Mohammed S.; Davis B. G. Angew. Chem. Int. Ed. 2016, 55, 8918. doi: 10.1002/anie.v55.31
[68]	Singh K.; Gupta J. K.; Kumar S.; Soni U. Curr. Protein Pept. Sci. 2024, 25, 507. doi: 10.2174/0113892037275221240327042353
[20]	Li J.; Wang J.; Wen L.; Zhu H.; Li S.; Huang K.; Jiang K.; Li X.; Ma C.; Qu J.; Parameswaran A.; Song J.; Zhao W.; Wang P. G. ACS Chem. Biol. 2016, 11, 3002. doi: 10.1021/acschembio.6b00678
[21]	Hart G. W.; Slawson C.; Ramirez-Correa G.; Lagerlof O. Annu. Rev. Biochem. 2011, 80, 825. doi: 10.1146/biochem.2011.80.issue-1
[22]	Wang Z.; Gucek M.; Hart G. W. Proc. Natl. Acad. Sci. U. S. A. 2008, 105, 13793. doi: 10.1073/pnas.0806216105
[23]	Kozeleková A.; Náplavová A.; Brom T.; Gašparik N.; Šimek J.; Houser J.; Hritz J. Front. Chem. 2022, 10, 835733. doi: 10.3389/fchem.2022.835733
[24]	Liu Y.; Yu K.; Kong X.; Zhang K.; Wang L.; Zhang N.; Chen Q.; Niu M.; Li W.; Zhong X.; Wu S.; Zhang J.; Liu Y. Sci. Adv. 2023, 9, eadg7112.
[25]	Ogawa M.; Tashima Y.; Sakaguchi Y.; Takeuchi H.; Okajima T. Biochem. Biophys. Res. Commun. 2020, 526, 184. doi: 10.1016/j.bbrc.2020.03.066
[69]	Mueller T.; Ouyang X.; Johnson M. S.; Qian W.-J.; Chatham J. C.; Darley-Usmar V.; Zhang J. Front. Aging 2021, 1, 620382. doi: 10.3389/fragi.2020.620382
[70]	Kim D. Y.; Park J.; Han I.-O. Am. J. Physiol. Cell Physiol. 2023, 325, C981.
[71]	Zhang J.; Kong G.; Yang J.; Pang L.; Li X. Eur. J. Med. Res. 2025, 30, 625. doi: 10.1186/s40001-025-02886-9
[72]	Liu F.; Shi J.; Tanimukai H.; Gu J.; Gu J.; Grundke-Iqbal I.; Iqbal K.; Gong C.-X. Brain 2009, 132, 1820. doi: 10.1093/brain/awp099
[73]	Liu F.; Iqbal K.; Grundke-Iqbal I.; Hart G. W.; Gong C.-X. Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 10804. doi: 10.1073/pnas.0400348101
[74]	Yuzwa S. A.; Macauley M. S.; Heinonen J. E.; Shan X.; Dennis R. J.; He Y.; Whitworth G. E.; Stubbs K. A.; McEachern E. J.; Davies G. J.; Vocadlo D. J. Nat. Chem. Biol. 2008, 4, 483. doi: 10.1038/nchembio.96
[26]	Kim Y. J.; Kang M. J.; Kim E.; Kweon T. H.; Park Y. S.; Ji S.; Yang W. H.; Yi E. C.; Cho J. W. Sci. Rep. 2020, 10, 19908. doi: 10.1038/s41598-020-76862-0
[27]	Ma Z.; Chalkley R. J.; Vosseller K. J. Biol. Chem. 2017, 292, 9150. doi: 10.1074/jbc.M116.766568
[28]	Maynard J. C.; Burlingame A. L.; Medzihradszky K. F. Mol. Cell. Proteomics 2016, 15, 3405. pmid: 27558639
[29]	De Leon C. A.; Levine P. M.; Craven T. W.; Pratt M. R. Biochemistry 2017, 56, 3507. doi: 10.1021/acs.biochem.7b00268
[30]	Tegl G.; Hanson J.; Chen H. M.; Kwan D. H.; Santana A. G.; Withers S. G. Angew. Chem. Int. Ed. 2019, 58, 1632. doi: 10.1002/anie.v58.6
[31]	Gorelik A.; Bartual S. G.; Borodkin V. S.; Varghese J.; Ferenbach A. T.; van Aalten D. M. Nat. Struct. Mol. Biol. 2019, 26, 1071. doi: 10.1038/s41594-019-0325-8 pmid: 31695185
[32]	Mitchell C. W.; Galan Bartual S.; Ferenbach A. T.; Scavenius C.; van Aalten D. M. Glycobiology 2023, 33, 1172. doi: 10.1093/glycob/cwad086 pmid: 37856504
[33]	Lee E. M.; Lee S. S.; Tripathi B. N.; Jung H. S.; Cao G. P.; Lee Y.; Singh S.; Hong S. H.; Lee K. W.; Lee S. Y.; Cho J.-Y.; Chung B. Y. Ann. Bot. 2015, 116, 713. doi: 10.1093/aob/mcv094
[34]	Davis L.; Chin J. W. Nat. Rev. Mol. Cell Biol. 2012, 13, 168. doi: 10.1038/nrm3286
[35]	Kaya E.; Gutsmiedl K.; Vrabel M.; Müller M.; Thumbs P.; Carell T. ChemBioChem 2009, 10, 2858. doi: 10.1002/cbic.v10:18
[36]	Liu H.; Wang L.; Brock A.; Wong C.-H.; Schultz P. G. J. Am. Chem. Soc. 2003, 125, 1702. doi: 10.1021/ja029433n
[37]	Yang B.; Wang N.; Schnier P. D.; Zheng F.; Zhu H.; Polizzi N. F.; Ittuveetil A.; Saikam V.; DeGrado W. F.; Wang Q.; Wang P. G.; Wang L. J. Am. Chem. Soc. 2019, 141, 7698. doi: 10.1021/jacs.9b02611
[38]	Gorelik A.; van Aalten D. M. RSC Chem. Biol. 2020, 1, 98. doi: 10.1039/D0CB00052C
[75]	Smet-Nocca C.; Broncel M.; Wieruszeski J.-M.; Tokarski C.; Hanoulle X.; Leroy A.; Landrieu I.; Rolando C.; Lippens G.; Hackenberger C. P. Mol. Biosyst. 2011, 7, 1420. doi: 10.1039/c0mb00337a pmid: 21327254
[76]	Brister M. A.; Pandey A. K.; Bielska A. A.; Zondlo N. J. J. Am. Chem. Soc. 2014, 136, 3803. doi: 10.1021/ja407156m
[77]	Ephrame S. J.; Cork G. K.; Marshall V.; Johnston M. A.; Shawa J.; Alghusen I.; Qiang A.; Denson A. R.; Carman M. S.; Fedosyuk H.; Swerdlow R. H.; Slawson C. Front. Aging Neurosci. 2023, 15, 1155630. doi: 10.3389/fnagi.2023.1155630
[78]	Borghgraef P.; Menuet C.; Theunis C.; Louis J. V.; Devijver H.; Maurin H.; Smet-Nocca C.; Lippens G.; Hilaire G.; Gijsen H.; Moechars D.; Leuven F. V. PLoS One 2013, 8, e84442.
[79]	Parra Bravo C.; Naguib S. A.; Gan L. Nat. Rev. Mol. Cell Biol. 2024, 25, 845. doi: 10.1038/s41580-024-00753-9
[80]	Aarsland D.; Batzu L.; Halliday G. M.; Geurtsen G. J.; Ballard C.; Ray Chaudhuri K.; Weintraub D. Nat. Rev. Dis. Primers 2021, 7, 47. doi: 10.1038/s41572-021-00280-3 pmid: 34210995
[81]	Levine P. M.; Galesic A.; Balana A. T.; Mahul-Mellier A.-L.; Navarro M. X.; De Leon C. A.; Lashuel H. A.; Pratt M. R. Proc. Natl. Acad. Sci. U. S. A. 2019, 116, 1511. doi: 10.1073/pnas.1808845116
[82]	Gong J.-Y.; Shang S.-Y.; Tan Z.-P. Chin. J. Biochem. Mol. Biol. 2024, 4, 409 (in Chinese).
	(巩金媛, 商世瑛, 谭忠平, 中国生物化学与分子生物学报, 2024, 4, 409.)
[83]	Gallardo J.; Escalona-Noguero C.; Sot B. ACS Chem. Neurosci. 2020, 11, 872. doi: 10.1021/acschemneuro.9b00527 pmid: 32078298
[84]	Marotta N. P.; Lin Y. H.; Lewis Y. E.; Ambroso M. R.; Zaro B. W.; Roth M. T.; Arnold D. B.; Langen R.; Pratt M. R. Nat. Chem. 2015, 7, 913. doi: 10.1038/nchem.2361
[85]	Lewis Y. E.; Galesic A.; Levine P. M.; De Leon C. A.; Lamiri N.; Brennan C. K.; Pratt M. R. ACS Chem. Biol. 2017, 12, 1020. doi: 10.1021/acschembio.7b00113 pmid: 28195695
[86]	Wu K.; Li D.; Xiu P.; Ji B.; Diao J. Phys. Biol. 2020, 18, 016002. doi: 10.1088/1478-3975/abb6dc
[87]	Levine P. M.; De Leon C. A.; Galesic A.; Balana A.; Marotta N. P.; Lewis Y. E.; Pratt M. R. Biorg. Med. Chem. 2017, 25, 4977. doi: 10.1016/j.bmc.2017.04.038
[39]	Antonczak A. K.; Simova Z.; Tippmann E. M. J. Biol. Chem. 2009, 284, 28795. doi: 10.1074/jbc.M109.027409 pmid: 19666472
[40]	Moon S. P.; Javed A.; Hard E. R.; Pratt M. R. JACS Au 2021, 2, 74. doi: 10.1021/jacsau.1c00455
[41]	Hamers-Casterman C.; Atarhouch T.; Muyldermans S. a.; Robinson G.; Hammers C.; Songa E. B.; Bendahman N.; Hammers R. Nature 1993, 363, 446. doi: 10.1038/363446a0
[42]	English H.; Hong J.; Ho M. Antibody Ther. 2020, 3, 1.
[43]	Jin B.-k.; Odongo S.; Radwanska M.; Magez S. Int. J. Mol. Sci. 2023, 24, 5994. doi: 10.3390/ijms24065994
[44]	Ramirez D. H.; Aonbangkhen C.; Wu H.-Y.; Naftaly J. A.; Tang S.; O’Meara T. R.; Woo C. M. ACS Chem. Biol. 2020, 15, 1059. doi: 10.1021/acschembio.0c00074 pmid: 32119511
[45]	Ge Y.; Ramirez D. H.; Yang B.; D’Souza A. K.; Aonbangkhen C.; Wong S.; Woo C. M. Nat. Chem. Biol. 2021, 17, 593. doi: 10.1038/s41589-021-00757-y
[88]	Zhang J.; Lei H.; Chen Y.; Ma Y.-T.; Jiang F.; Tan J.; Zhang Y.; Li J.-D. Neurosci. Lett. 2017, 655, 90. doi: 10.1016/j.neulet.2017.06.034
[89]	Javed A.; Johnson O. T.; Balana A. T.; Volk R. F.; Langen A.; Ahn B. S.; Zaro B. W.; Gestwicki J. E.; Pratt M. R. Protein Sci. 2024, 33, e5173.
[90]	Permanne B.; Sand A.; Ousson S.; Nény M.; Hantson J.; Schubert R.; Wiessner C.; Quattropani A.; Beher D. ACS Chem. Neurosci. 2022, 13, 1296. doi: 10.1021/acschemneuro.2c00057 pmid: 35357812
[91]	Wani W. Y.; Ouyang X.; Benavides G. A.; Redmann M.; Cofield S. S.; Shacka J. J.; Chatham J. C.; Darley-Usmar V.; Zhang J. Mol. Brain 2017, 10, 32. doi: 10.1186/s13041-017-0311-1
[92]	Balana A. T.; Mahul-Mellier A.-L.; Nguyen B. A.; Horvath M.; Javed A.; Hard E. R.; Jasiqi Y.; Singh P.; Afrin S.; Pedretti R.; Singh V.; Lee V. M.-Y.; Luk K. C.; Saelices L.; Lashuel H. A.; Pratt M. R. Nat. Chem. Biol. 2024, 20, 646. doi: 10.1038/s41589-024-01551-2 pmid: 38347213
[93]	Bomont P. Curr. Opin. Cell Biol. 2021, 68, 181. doi: 10.1016/j.ceb.2020.10.011
[94]	Stone E. J.; Kolb S. J.; Brown A. Cytoskeleton 2021, 78, 97. doi: 10.1002/cm.v78.3
[95]	Moon S. P.; Wang B.; Ahn B. S.; Ryu A. H.; Hard E. R.; Javed A.; Pratt M. R. ACS Chem. Biol. 2023, 18, 1705. doi: 10.1021/acschembio.3c00292
[96]	Huynh D. T.; Tsolova K. N.; Watson A. J.; Khal S. K.; Green J. R.; Li D.; Hu J.; Soderblom E. J.; Chi J.-T.; Evans C. S. Nat. Commun. 2023, 14, 6558. doi: 10.1038/s41467-023-42227-0 pmid: 37848414
[97]	Pavlova N. N.; Thompson C. B. Cell Metab. 2016, 23, 27. doi: 10.1016/j.cmet.2015.12.006
[98]	DeBerardinis R. J.; Chandel N. S. Sci. Adv. 2016, 2, e1600200.
[99]	Huo C.-X.; Zheng X.-J.; Liu C.-C.; Song C.; Xiao A.; Sun S.; Lyu Z.; Geng Y.; Ye X.-S. Glycoscience & Therapy 2025, 100006.
[100]	Chinta S.; Sonali L.; Pavithra R.; Raj M. D.; Kanimozhi N.; Sukumar M. Glycoscience & Therapy 2025, 100004.
[101]	Lu Q.; Zhang X.; Liang T.; Bai X. Mol. Med. 2022, 28, 115. doi: 10.1186/s10020-022-00544-y
[102]	Shi Y.; Tomic J.; Wen F.; Shaha S.; Bahlo A.; Harrison R.; Dennis J.; Williams R.; Gross B.; Walker S.; Zuccolo J.; Deans J. P.; Hart G. W.; Spaner D. E. Leukemia 2010, 24, 1588. doi: 10.1038/leu.2010.152 pmid: 20668475
[103]	Schauner R.; Cress J.; Hong C.; Wald D.; Ramakrishnan P. Front. Immunol. 2024, 15, 1327405. doi: 10.3389/fimmu.2024.1327405
[104]	Wells L.; Hart G. W. J. Biol. Chem. 2024, 300, 107635. doi: 10.1016/j.jbc.2024.107635
[105]	Ma X.; Fu H.; Sun C.; Wu W.; Hou W.; Zhou Z.; Zheng H.; Gong Y.; Wu H.; Qin J.; Lou H.; Li N.; Tang T.-S.; Guo C. Cell Death Dis. 2024, 15, 321. doi: 10.1038/s41419-024-06700-y
[106]	Xue J.-J.; Sun H. Chin. J. Biochem. Mol. Biol. 2024, 4, 474 (in Chinese).
	(薛俊杰, 孙慧, 中国生物化学与分子生物学报, 2024, 4, 474.)
[107]	Lei Y.; Chen T.; Li Y.; Shang M.; Zhang Y.; Jin Y.; Yu Q.; Guo F.; Wang T. Oncogenesis 2020, 9, 21. doi: 10.1038/s41389-020-0208-1
[108]	Wang Y.; Liu J.; Jin X.; Zhang D.; Li D.; Hao F.; Feng Y.; Gu S.; Meng F.; Tian M.; Zheng Y.; Xin L.; Zhang X.; Han X.; Aravind L.; Wei M. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, 13732. doi: 10.1073/pnas.1704145115
[109]	Singh J. P.; Qian K.; Lee J.-S.; Zhou J.; Han X.; Zhang B.; Ong Q.; Ni W.; Jiang M.; Ruan H.-B.; Li M.-D.; Zhang K.; Ding Z.; Lee P.; Singh K.; Wu J.; Herzog R. I.; Kaech S.; Wendel H.-G.; Yates III J. R.; Han W.; Sherwin R. S.; Nie Y.; Yang X. Oncogene 2020, 39, 560. doi: 10.1038/s41388-019-0975-3
[110]	Zhou Z.; Zheng X.; Zhao J.; Yuan A.; Lv Z.; Shao G.; Peng B.; Dong M.-Q.; Xu Q.; Xu X.; Li J. Oncogene 2024, 43, 1769. doi: 10.1038/s41388-024-03035-y
[111]	Nie H.; Ju H.; Fan J.; Shi X.; Cheng Y.; Cang X.; Zheng Z.; Duan X.; Yi W. Nat. Commun. 2020, 11, 36. doi: 10.1038/s41467-019-13601-8
[112]	Ma X.; Liu H.; Li J.; Wang Y.; Ding Y.-H.; Shen H.; Yang Y.; Sun C.; Huang M.; Tu Y.; Liu Y.; Zhao Y.; Dong M.-Q.; Xu P.; Tang T.-S.; Guo C. Nat. Commun. 2017, 8, 1941. doi: 10.1038/s41467-017-02164-1
[113]	Zhou Y.; Zhang Y.; Peng C.; Li Z.; Pei H.; Pei H.; Zhu W. Clin. Transl. Med. 2022, 12, e785.
[114]	Tian Y.; Zhu Q.; Sun Z.; Geng D.; Lin B.; Su X.; He J.; Guo M.; Xu H.; Zhao Y.; Qin W.; Wang P. G.; Wen L.; Yi W. Angew. Chem. Int. Ed. 2021, 60, 26128. doi: 10.1002/anie.v60.50
[115]	Liu Y.; Yu K.; Zhang K.; Niu M.; Chen Q.; Liu Y.; Wang L.; Zhang N.; Li W.; Zhong X. EMBO Rep. 2023, 24, e56458.
[116]	Li J.; Liu X.; Peng B.; Feng T.; Zhou W.; Meng L.; Zhao S.; Zheng X.; Wu C.; Wu S.; Chen X.; Xu X.; Sun J.; Li J. J. Biol. Chem. 2023, 299, 105354. doi: 10.1016/j.jbc.2023.105354
[117]	Liu Y.; Chen Q.; Zhang N.; Zhang K.; Dou T.; Cao Y.; Liu Y.; Li K.; Hao X.; Xie X. Nat. Commun. 2020, 11, 5898. doi: 10.1038/s41467-020-19579-y
[118]	Xie X.; Wu Q.; Zhang K.; Liu Y.; Zhang N.; Chen Q.; Wang L.; Li W.; Zhang J.; Liu Y. Biochim. Biophys. Acta, Gen. Subj. 2021, 1865, 129930. doi: 10.1016/j.bbagen.2021.129930
[119]	Zhang Y.; Zhou S.; Kai Y.; Zhang Y.-q.; Peng C.; Li Z.; Mughal M. J.; Julie B.; Zheng X.; Ma J. Nat. Commun. 2024, 15, 5597. doi: 10.1038/s41467-024-49875-w pmid: 38961064
[120]	Qin W.; Lv P.; Fan X.; Quan B.; Zhu Y.; Qin K.; Chen Y.; Wang C.; Chen X. Proc. Natl. Acad. Sci. U. S. A. 2017, 114, E6749.
[121]	Qian L.; Yang X.; Li S.; Zhao H.; Gao Y.; Zhao S.; Lv X.; Zhang X.; Li L.; Zhai L. Cell Death Discovery 2021, 7, 112. doi: 10.1038/s41420-021-00489-x
[122]	Luanpitpong S.; Angsutararux P.; Samart P.; Chanthra N.; Chanvorachote P.; Issaragrisil S. Sci. Rep. 2017, 7, 10607. doi: 10.1038/s41598-017-10886-x pmid: 28878262
[123]	Yan T.; Ma X.; Zhou K.; Cao J.; Tian Y.; Zheng H.; Tong Y.; Xie S.; Wang Y.; Guo L. Int. J. Biol. Sci. 2024, 20, 1279. doi: 10.7150/ijbs.89700
[124]	Huang X.; Pan Q.; Sun D.; Chen W.; Shen A.; Huang M.; Ding J.; Geng M. J. Biol. Chem. 2013, 288, 36418. doi: 10.1074/jbc.M113.495713 pmid: 24214978
[125]	Liu Y.-Y.; Liu H.-Y.; Yu T.-J.; Lu Q.; Zhang F.-L.; Liu G.-Y.; Shao Z.-M.; Li D.-Q. Cell Death Differ. 2022, 29, 861. doi: 10.1038/s41418-021-00901-0
[126]	Zhu G.; Tao T.; Zhang D.; Liu X.; Qiu H.; Han L.; Xu Z.; Xiao Y.; Cheng C.; Shen A. Glycobiology 2016, 26, 820. doi: 10.1093/glycob/cww025
[127]	Ge X.; Peng X.; Li M.; Ji F.; Chen J.; Zhang D. Pathol. Res. Pract. 2021, 225, 153580. doi: 10.1016/j.prp.2021.153580
[128]	Lima J. E.; Moreira N. C.; Sakamoto-Hojo E. T. Mutat. Res. - Genet. Toxicol. Environ. Mutagen. 2022, 874, 503437.
[129]	Lu X.; Xie Q.; Pan X.; Zhang R.; Zhang X.; Peng G.; Zhang Y.; Shen S.; Tong N. Signal Transduct. Target. Ther. 2024, 9, 262.
[130]	Cheng S. S.; Mody A. C.; Woo C. M. Chem. Rev. 2024, 124, 12918. doi: 10.1021/acs.chemrev.4c00417
[131]	Accili D.; Deng Z.; Liu Q. Nat. Rev. Endocrinol. 2025, 21, 7.
[132]	Yang X.; Ongusaha P. P.; Miles P. D.; Havstad J. C.; Zhang F.; So W. V.; Kudlow J. E.; Michell R. H.; Olefsky J. M.; Field S. J. Nature 2008, 451, 964. doi: 10.1038/nature06668
[133]	Park S. Y.; Ryu J.; Lee W. Exp. Mol. Med. 2005, 37, 220. doi: 10.1038/emm.2005.30
[134]	Wang X.; Feng Z.; Wang X.; Yang L.; Han S.; Cao K.; Xu J.; Zhao L.; Zhang Y.; Liu J. Diabetologia 2016, 59, 1287. doi: 10.1007/s00125-016-3919-2 pmid: 26993634
[135]	Cooksey R. C.; Pusuluri S.; Hazel M.; McClain D. A. Am. J. Physiol. Endocrinol. Metab. 2006, 290, E334.
[136]	Yang Y.; Fu M.; Li M.-D.; Zhang K.; Zhang B.; Wang S.; Liu Y.; Ni W.; Ong Q.; Mi J. Nat. Commun. 2020, 11, 181. doi: 10.1038/s41467-019-13914-8
[137]	Keembiyehetty C.; Love D. C.; Harwood K. R.; Gavrilova O.; Comly M. E.; Hanover J. A. J. Biol. Chem. 2015, 290, 7097. doi: 10.1074/jbc.M114.617779 pmid: 25596529
[138]	Zraika S.; Dunlop M.; Proietto J.; Andrikopoulos S. Arch. Biochem. Biophys. 2002, 405, 275. doi: 10.1016/S0003-9861(02)00397-1
[139]	Akimoto Y.; Hart G. W.; Wells L.; Vosseller K.; Yamamoto K.; Munetomo E.; Ohara-Imaizumi M.; Nishiwaki C.; Nagamatsu S.; Hirano H. Glycobiology 2007, 17, 127. doi: 10.1093/glycob/cwl067
[140]	Wu L.-X.; Xu Y.-C.; Pantopoulos K.; Tan X.-Y.; Wei X.-L.; Zheng H.; Luo Z. J. Nutr. Biochem. 2023, 117, 109337. doi: 10.1016/j.jnutbio.2023.109337
[141]	Housley M. P.; Rodgers J. T.; Udeshi N. D.; Kelly T. J.; Shabanowitz J.; Hunt D. F.; Puigserver P.; Hart G. W. J. Biol. Chem. 2008, 283, 16283. doi: 10.1074/jbc.M802240200
[142]	Andersen A.; Lund A.; Knop F. K.; Vilsbøll T. Nat. Rev. Endocrinol. 2018, 14, 390. doi: 10.1038/s41574-018-0016-2 pmid: 29728598
[143]	Zhao Y.; Tang Z.; Shen A.; Tao T.; Wan C.; Zhu X.; Huang J.; Zhang W.; Xia N.; Wang S. Int. J. Mol. Sci. 2015, 16, 22856. doi: 10.3390/ijms160922856 pmid: 26402673
[144]	Kaleem A.; Javed S.; Rehman N.; Abdullah R.; Iqtedar M.; Aftab M. N.; Hoessli D. C.; Haq I.-U. Protein Pept. Lett. 2021, 28, 333. doi: 10.2174/0929866527666200813210407

靶向特定蛋白质的O-GlcNAc修饰精准调控工具:疾病机制研究与治疗机遇

Tools for Precise Control of Protein-Specific O-GlcNAcylation: Insights into Disease Mechanisms and Therapeutic Opportunities

RichHTML

PDF

Knowledge

Abstract

Cite this article

share this article

Fig. & Tab. 10

References 144

Related Articles 1

Recommended Articles

Metrics

Comments