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N-deglycosylation targeting chimera (DGlyTAC): a strategy for immune checkpoint proteins inactivation by specifically removing N-glycan

Authors: Li Li,Jiajia Wu,Weiqian Cao,Wei Zhang,Qi Wu,Yaxu Li,Yanrong Yang,Zezhi Shan,Zening Zheng,Xin Ge,Liang Lin,Ping Wang
Publisher: Springer Science and Business Media LLC
Publish date: 2025-4-28
ISSN: 2059-3635 DOI: 10.1038/s41392-025-02219-6
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1. Could you clarify how “de-N-glycosylation efficiency” was quantified in Fig. 6e–f? Specifically, how were glycoforms with <4 N-glycans distinguished from fully glycosylated forms on immunoblots, and was this classification validated with complementary techniques?

2. In Fig. 3j–l, you report a ~16-fold reduction in PD-1 binding to PD-L1 after treatment with nbhPDL1-PNGF. How was this fold change calculated from flow cytometry data, and was the binding inhibition confirmed by a quantitative biophysical method such as SPR or ITC? Additionally, how do you interpret the remaining PD-1 binding despite near-complete deglycosylation?

3. Although nbmPDL1-PNGF accumulates in non-tumor tissues such as liver and kidney (Fig. 6), you report little to no off-target deglycosylation. Could you elaborate on how you distinguished protein accumulation from enzymatic activity, and whether any assessment was done for potential deglycosylation of other endogenous glycoproteins in those organs?

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