amides, metabolism, animals, cell line, tumor, cricetinae, glycopeptides, glycoproteins, glycosylation, insulin
Deamidation has been recognized as a common spontaneous pathway of protein degradation and a prevalent concern in the pharmaceutical industry; deamidation caused the reduction of protein/peptide drug efficacy and shelf life in several cases. More importantly, deamidation of physiological proteins is related to several human diseases and considered a "timer" for the diseases. N-linked glycosylation has a variety of significant biological functions, and it interestingly occurs right on the deamidation site-asparagine. It has been perceived that N-glycosylation could prevent deamidation, but experimental support is still lacking for clearly understanding the role of N-glycosylation on deamidation. Our results presented that deamidation is prevented by naturally occurring N-linked glycosylation. Glycopeptides and corresponding nonglycosylated peptides were used to compare their deamidation rates. All the nonglycosylated peptides have different half-lives ranging from one to 20 days, for the corresponding glycosylated peptides; all the results showed that the deamidation reaction was significantly reduced by the introduction of N-linked glycosylation. A glycoprotein, RNase B, also showed a significantly elongated deamidation half-life compared to nonglycosylated protein RNase A. At last, N-linked glycosylation on INGAP-P, a therapeutic peptide, increased the deamidation half-life of INGAP-P as well as its therapeutic potency.
Source Publication Title
ACS Chemical Biology
American Chemical Society
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Zhu, J., Liu, D., Tran, V. P., Wu, Z., Jiang, K., Zhu, H., Zhang, J., Gibbons, C., Xue, B., Shi, H., & Wang, P. G. (2020). N‑Linked Glycosylation Prevents Deamidation of Glycopeptide and Glycoprotein. ACS Chemical Biology, 15 (12), 3197. https://doi.org/10.1021/acschembio.0c00734