A Hydroxylamine-Mediated Amidination of Lysine Residues That Retains the Protein's Positive Charge
Pei-Yang He
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorYusai Zhou
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorPu-Guang Chen
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorMeng-Qian Zhang
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorJin-Jian Hu
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorYeh-Jun Lim
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorProf. Hongjie Zhang
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Kai Liu
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Yan-Mei Li
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Beijing Institute for Brain Disorders, Beijing, 100069 P. R. China
Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorPei-Yang He
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorYusai Zhou
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorPu-Guang Chen
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorMeng-Qian Zhang
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Authors contributed equally.
Search for more papers by this authorJin-Jian Hu
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorYeh-Jun Lim
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorProf. Hongjie Zhang
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Kai Liu
Engineering Research Center of Advanced Rare Earth Materials, (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorCorresponding Author
Prof. Yan-Mei Li
Key Laboratory of Bioorganic Phosphorus Chemistry and Chemical Biology, Ministry of Education, Department of Chemistry, Tsinghua University, Beijing, 100084 P. R. China
Beijing Institute for Brain Disorders, Beijing, 100069 P. R. China
Center for Synthetic and Systems Biology, Tsinghua University, Beijing, 100084 P. R. China
Search for more papers by this authorAbstract
Lysine-specific peptide and protein modification strategies are widely used to study charge-related functions and applications. However, these strategies often result in the loss of the positive charge on lysine, significantly impacting the charge-related properties of proteins. Herein, we report a strategy to preserve the positive charge and selectively convert amines in lysine side chains to amidines using nitriles and hydroxylamine under aqueous conditions. Various unprotected peptides and proteins were successfully modified with a high conversion rate. Moreover, the reactive amidine moiety and derived modification site enable subsequent secondary modifications. Notably, positive charges were retained during the modification. Therefore, positive charge-related protein properties, such as liquid-liquid phase separation behaviour of α-synuclein, were not affected. This strategy was subsequently applied to a lysine rich protein to develop an amidine-containing coacervate DNA complex with outstanding mechanical properties. Overall, our innovative strategy provides a new avenue to explore the characteristics of positively charged proteins.
Conflict of interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
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