Citation: Jiaxu Zhang, Xianran He, Gilles Clodic, Leyu Tang, Jinge Cao, Yupeng Fu, Matthieu Sollogoub, Yongmin Zhang. Anomeric configuration controls reductive amination efficiency: Structural and electronic insights into protein-monosaccharide conjugation[J]. Chinese Chemical Letters, ;2026, 37(8): 112033. doi: 10.1016/j.cclet.2025.112033 shu

Anomeric configuration controls reductive amination efficiency: Structural and electronic insights into protein-monosaccharide conjugation

Jiaxu Zhang ^{a, b} ,
Xianran He ^a ,
Gilles Clodic ^a ,
Leyu Tang ^a ,
Jinge Cao ^a ,
Yupeng Fu ^a ,
Matthieu Sollogoub ^a ,
Yongmin Zhang ^{a, b, c, *,}

a.
Institut Parisien de Chimie Moléculaire, CNRS UMR8232, Sorbonne Université, 4 Place Jussieu, Paris 75005, France
b.
Translational Research Institute for Dermatology and Cosmetics, School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou 510006, China
c.
Fuyang Institute & School of Pharmaceutical Sciences, Zhejiang Chinese Medical University, Hangzhou 310061, China

yongmin.zhang@upmc.fr

Received Date: 23 July 2025
Revised Date: 14 October 2025
Accepted Date: 29 October 2025
Available Online: 29 October 2025

Figures(5)

Reductive amination between glycolaldehyde derivatives and lysine residues is a widely used strategy for constructing neoglycoproteins in biomedical applications. Here, α- and β-glycolaldehyde glycosides of five biologically relevant monosaccharides (Glc, Gal, Man, GlcNAc, GalNAc) were synthesized and conjugated to protein at a fixed sugar-to-protein ratio. Continuous kinetic monitoring revealed that anomeric configuration markedly influences both reaction rates and final sugar loading: α-Man > β-Man; β-Gal/GalNAc > their α-counterparts; Glc and GlcNAc showed no significant anomeric preferences. NMR analysis identified cyclic intermediates that reduce the effective concentration of reactive aldehyde, while DFT calculations provided complementary insight into anomer-specific electrophilic character. These findings offer a mechanistic rationale for selecting anomeric configuration in glycoconjugate design.
- Reductive amination,
- Glycoconjugation,
- Neoglycoprotein,
- Stereochemistry,
- Glycosidic functionalization
1. [1]
  S. Albrecht, S. Vainauskas, H. Stöckmann, C. McManus, C.H. Taron, P.M. Rudd, Anal. Chem. 88 (2016) 4795–4802. doi: 10.1021/acs.analchem.6b00259
2. [2]
  A. Peixoto, A. Miranda, L.L. Santos, J.A. Ferreira, J. Exp. Clin. Canc. Res. 41 (2022) 143. doi: 10.1186/s13046-022-02335-z
3. [3]
  C. Sorieul, F. Papi, F. Carboni, et al., Pharmacol. Therapeut. 235 (2022) 108158. doi: 10.1016/j.pharmthera.2022.108158
4. [4]
  S.S. Shivatare, V.S. Shivatare, C.H. Wong, Chem. Rev. 122 (2022) 15603–15671. doi: 10.1021/acs.chemrev.1c01032
5. [5]
  J. Zhang, M. Terreni, F. Liu, M. Sollogoub, Y. Zhang, Biomed. Pharmacother. 176 (2024) 116824. doi: 10.1016/j.biopha.2024.116824
6. [6]
  C. Song, X. Zheng, H. Guo, et al., Glycoconjugate J. 36 (2019) 399–408. doi: 10.1007/s10719-019-09884-0
7. [7]
  C. Song, S. Sun, C. Huo, et al., Bioorgan. Med. Chem. 24 (2016) 915–920. doi: 10.1016/j.bmc.2016.01.015
8. [8]
  Y. Pan, P. Chefalo, N. Nagy, C. Harding, Z. Guo, J. Med. Chem. 48 (2005) 875–883. doi: 10.1021/jm0494422
9. [9]
  Q. Wang, S.A. Ekanayaka, J. Wu, J. Zhang, Z. Guo, Bioconjugate Chem. 19 (2008) 2060–2067. doi: 10.1021/bc800243f
10. [10]
  J.C. Gildersleeve, O. Oyelaran, J.T. Simpson, B. Allred, Bioconjugate Chem. 19 (2008) 1485–1490. doi: 10.1021/bc800153t
11. [11]
  S.A. Malaker, M.J. Ferracane, F.R. Depontieu, et al., J. Proteome. Res. 16 (2017) 228–237. doi: 10.1021/acs.jproteome.6b00496
12. [12]
  J.A. Speir, U.M. Abdel-Motal, M. Jondal, I.A. Wilson, Immunity 10 (1999) 51–61. doi: 10.1016/S1074-7613(00)80006-0
13. [13]
  L.P. Deimel, X. Xue, A. Khan, et al., bioRxiv (2023), doi:10.1101/2023.11.02. 565155. doi: 10.1101/2023.11.02.565155
14. [14]
  T. Buskas, Y. Li, G.J. Boons, Chem. Eur. J. 10 (2004) 3517–3524. doi: 10.1002/chem.200400074
15. [15]
  S. Sun, X. Zheng, C. Huo, et al., ChemMedChem 11 (2016) 1090–1096. doi: 10.1002/cmdc.201600094
16. [16]
  X. Wu, H. McFall-Boegeman, Z. Rashidijahanabad, et al., Org. Biomol. Chem. 19 (2021) 2448–2455. doi: 10.1039/d1ob00007a
17. [17]
  X. Zheng, F. Yang, M. Zheng, et al., Org. Biomol. Chem. 13 (2015) 6399–6406. doi: 10.1039/C5OB00405E
18. [18]
  C. Song, X. Zheng, C. Liu, Y. Zhou, X. Ye, Oncotarget 8 (2017) 47330–47343. doi: 10.18632/oncotarget.17646
19. [19]
  T.T. Fang, B. Bendiak, J. Am. Chem. Soc. 129 (2007) 9721–9736. doi: 10.1021/ja0717313
20. [20]
  L. Jäntschi, App. Water Sci. 9 (2019) 1–11.
21. [21]
  Y. Zhong, B.A. Bauer, S. Patel, J. Comput. Chem. 32 (2011) 3339–3353. doi: 10.1002/jcc.21873
22. [22]
  M. Mohan, V.V. Goud, T. Banerjee, Fluid. Phase Equilib. 395 (2015) 33–43. doi: 10.1016/j.fluid.2015.03.020
23. [23]
  J.J. Reina, A. Rioboo, J. Montenegro, Synthesis 50 (2018) 831–845. doi: 10.1055/s-0036-1591082
24. [24]
  J.L. Dashnau, K.A. Sharp, J.M. Vanderkooi, J. Phys. Chem. B. 109 (2005) 24152–24159. doi: 10.1021/jp0543072
25. [25]
  K. Adjir, M. Sekkal-Rahal, M. Springborg, J. Biomol. Struct. Dyn. 41 (2023) 5981–5989. doi: 10.1080/07391102.2022.2099975
26. [26]
  B.L. Foley, M.B. Tessier, R.J. Woods, Wires. Comput. Mol. Sci. 2 (2012) 652–697. doi: 10.1002/wcms.89
1. [1]
  Xiuhua Wang , Jianrong Steve Zhou . A dicationic nickel complex-catalyzed asymmetric synthesis of chiral benzylic amines: Evolution from reductive amination to borrowing hydrogen reaction. Chinese Chemical Letters, 2026, 37(2): 111148-. doi: 10.1016/j.cclet.2025.111148
2. [2]
  Min Fu , Pan He , Sen Zhou , Wenqiang Liu , Bo Ma , Shiying Shang , Yaohao Li , Ruihan Wang , Zhongping Tan . An unexpected stereochemical effect of thio-substituted Asp in native chemical ligation. Chinese Chemical Letters, 2024, 35(8): 109434-. doi: 10.1016/j.cclet.2023.109434
3. [3]
  Hong Lu , Yidie Zhai , Xingxing Cheng , Yujia Gao , Qing Wei , Hao Wei . Advancements and Expansions in the Proline-Catalyzed Asymmetric Aldol Reaction. University Chemistry, 2024, 39(5): 154-162. doi: 10.3866/PKU.DXHX202310074
4. [4]
  Siwen Yuan , Qilin Wu , TianpengYin . NMR Spectroscopy Teaching Design Using the Mosher Method for Stereochemistry of Organic Compounds Based on BOPPPS Teaching Model. University Chemistry, 2025, 40(7): 161-168. doi: 10.12461/PKU.DXHX202502073
5. [5]
  Yuena Yu , Fang Fang . Microwave-Assisted Synthesis of Safinamide Methanesulfonate. University Chemistry, 2024, 39(11): 210-216. doi: 10.3866/PKU.DXHX202401076
6. [6]
  Pengcheng Su , Shizheng Chen , Zhihong Yang , Ningning Zhong , Chenzi Jiang , Wanbin Li . Vapor-phase postsynthetic amination of hypercrosslinked polymers for efficient iodine capture. Chinese Chemical Letters, 2024, 35(9): 109357-. doi: 10.1016/j.cclet.2023.109357
7. [7]
  Huiying LIN , Xiang ZHAO , Banghao WEI , Bufeng WANG , Zhiyong LU , Junfeng BAI . Perfluroalkane functionalization on MOF-808 for acetylene purification. Chinese Journal of Inorganic Chemistry, 2025, 41(10): 2103-2114. doi: 10.11862/CJIC.20250110
8. [8]
  Xiao-Bo Liu , Ren-Ming Liu , Xiao-Di Bao , Hua-Jian Xu , Qi Zhang , Yu-Feng Liang . Nickel-catalyzed reductive formylation of aryl halides via formyl radical. Chinese Chemical Letters, 2024, 35(12): 109783-. doi: 10.1016/j.cclet.2024.109783
9. [9]
  Saima Perveen , Xicheng Wang , Tao Li , Linghua Wang , Shuai Zhang , Yizhao Ouyang , Xue Zhao , Liang Xu , Pengfei Li . Enantioconvergent reductive amidation of benzyl ammonium salts for synthesis of α-chiral amides. Chinese Chemical Letters, 2026, 37(1): 111779-. doi: 10.1016/j.cclet.2025.111779
10. [10]
  Wen-Tao Ouyang , Jun Jiang , Yan-Fang Jiang , Ting Li , Yuan-Yuan Liu , Hong-Tao Ji , Li-Juan Ou , Wei-Min He . Sono-photocatalytic amination of quinoxalin-2(1H)-ones with aliphatic amines. Chinese Chemical Letters, 2024, 35(10): 110038-. doi: 10.1016/j.cclet.2024.110038
11. [11]
  Chong-Yang Shi , Jian-Xing Gong , Zhen Li , Chao Shu , Long-Wu Ye , Qing Sun , Bo Zhou , Xin-Qi Zhu . Gold-catalyzed intermolecular amination of allyl azides with ynamides: Efficient construction of 3-azabicyclo[3.1.0] scaffold. Chinese Chemical Letters, 2025, 36(2): 109895-. doi: 10.1016/j.cclet.2024.109895
12. [12]
  Wen-Jing Li , Jun-Bo Wang , Yu-Heng Liu , Mo Zhang , Zhan-Hui Zhang . Molybdenum-doped carbon nitride as an efficient heterogeneous catalyst for direct amination of nitroarenes with arylboronic acids. Chinese Chemical Letters, 2025, 36(3): 110001-. doi: 10.1016/j.cclet.2024.110001
13. [13]
  Haoquan Huang , Haiting Chen , Xinran Dong , Yanbin Xu , Anlian Huang , Qiaoyi Cen , Huairou Zhu , Guosheng Chen , Wei Yi , Siming Huang , Gangfeng Ouyang . Site-specific surface amination strategy facilitates biomimetic encapsulation of enzymes within hydrogen-bonded organic framework. Chinese Chemical Letters, 2025, 36(9): 111223-. doi: 10.1016/j.cclet.2025.111223
14. [14]
  Hong Xin , Shutao Wang , Li-Na Guo , Cheng Guan , Jinyi Liao , Zi-Hang Yuan , Zhengze Zhang , Xin-Hua Duan . An unusual carbon radical-mediated ring-opening/amination or esterification cascade of unstrained α-haloalkyl cycloketone derivatives. Chinese Chemical Letters, 2026, 37(7): 111939-. doi: 10.1016/j.cclet.2025.111939
15. [15]
  Guanxiong Yu , Chengkai Xu , Huaqiang Ju , Jie Ren , Guangpeng Wu , Chengjian Zhang , Xinghong Zhang , Zhen Xu , Weipu Zhu , Hao-Cheng Yang , Haoke Zhang , Jianzhao Liu , Zhengwei Mao , Yang Zhu , Qiao Jin , Kefeng Ren , Ziliang Wu , Hanying Li . Key progresses of MOE key laboratory of macromolecular synthesis and functionalization in 2023. Chinese Chemical Letters, 2024, 35(11): 109893-. doi: 10.1016/j.cclet.2024.109893
16. [16]
  Giulia Brufani , Edoardo Bazzica , Yanlong Gu , Francesco Mauriello , Luigi Vaccaro . Csp²–H functionalization as an efficient catalytic route to carbazoles. Chinese Chemical Letters, 2026, 37(1): 111545-. doi: 10.1016/j.cclet.2025.111545
17. [17]
  Kangyuan Xie , Tianxiang Fang , Qingli Zhu , Qingyang Xu , Boyu Peng , Guangpeng Wu , Chao Gao , Haocheng Yang , Liping Zhu , Hongqing Liang , Weipu Zhu , Peng Zhang , Qiao Jin , Zhengwei Mao , Kefeng Ren , Yang Zhu , Haoke Zhang , Ziliang Wu , Chao Zhang , Hanying Li . Key progresses of MOE Key laboratory of macromolecular synthesis and functionalization in 2024. Chinese Chemical Letters, 2026, 37(2): 111990-. doi: 10.1016/j.cclet.2025.111990
18. [18]
  Ping Zhang , Hongyuan Ren , Zhaofeng Sun , Hou-Ji Cao , Deshuang Tu , Chang-Sheng Lu , Jordi Poater , Miquel Solà , Hong Yan . Facile and regioselective B–H bond functionalization of carboranes via cage···Ⅰ(Ⅲ) interaction. Chinese Chemical Letters, 2026, 37(5): 111617-. doi: 10.1016/j.cclet.2025.111617
19. [19]
  Junxin Li , Chao Chen , Yuzhen Dong , Jian Lv , Jun-Mei Peng , Yuan-Ye Jiang , Daoshan Yang . Ligand-promoted reductive coupling between aryl iodides and cyclic sulfonium salts by nickel catalysis. Chinese Chemical Letters, 2024, 35(11): 109732-. doi: 10.1016/j.cclet.2024.109732
20. [20]
  Li Li , Zhi-Xin Yan , Chuan-Kun Ran , Yi Liu , Shuo Zhang , Tian-Yu Gao , Long-Fei Dai , Li-Li Liao , Jian-Heng Ye , Da-Gang Yu . Electro-reductive carboxylation of CCl bonds in unactivated alkyl chlorides and polyvinyl chloride with CO₂. Chinese Chemical Letters, 2024, 35(12): 110104-. doi: 10.1016/j.cclet.2024.110104

Get Citation

PDF

XML

Metrics

PDF Downloads(0)
Abstract views(17)
HTML views(0)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142