By investigating 17 peptide arylthioesters that were previously challenging to produce,this study reveals a clear correlation between increased ligation activity and decreased pKa values of their corresponding arylthi...By investigating 17 peptide arylthioesters that were previously challenging to produce,this study reveals a clear correlation between increased ligation activity and decreased pKa values of their corresponding arylthiols.The observed differences are attributed to variations in thioester bond strength and steric hindrance.These insights have led to the development of an improved one-pot chemical protein synthesis approach that leverages the reactivity differences between peptide arylthioesters with C-terminal Ala-SPh(4-NO_(2))and Ala-S-Ph(2,6-diCH_(3)).This approach eliminates the need for thiol-thioester exchange and additive removal steps while enabling in situ desulfurization,thereby significantly simplifying the protein synthesis process.展开更多
基金CAMS Innovation Fund for Medical Sciences(CIFMS,No.2021-I2M-1-026)the National Key R&D Program of China(No.2018YFE0111400)+6 种基金the NIH Research Project Grant Program(No.R01 EB025892)the National Natural Science Foundation of China(the Training Program of the Major Research Plan,No.91853120)the National Major Scientific and Technological Special Project of China(Nos.2018ZX09711001-005 and 2018ZX09711001-013)the State Key Laboratory of Bioactive Substance and Function of Natural Medicines,Institute of Materia Medicathe Biomedical High Performance Computing Platform,Chinese Academy of Medical Sciencesthe Chinese Academy of Medical SciencesPeking Union Medical College for funding and support.
文摘By investigating 17 peptide arylthioesters that were previously challenging to produce,this study reveals a clear correlation between increased ligation activity and decreased pKa values of their corresponding arylthiols.The observed differences are attributed to variations in thioester bond strength and steric hindrance.These insights have led to the development of an improved one-pot chemical protein synthesis approach that leverages the reactivity differences between peptide arylthioesters with C-terminal Ala-SPh(4-NO_(2))and Ala-S-Ph(2,6-diCH_(3)).This approach eliminates the need for thiol-thioester exchange and additive removal steps while enabling in situ desulfurization,thereby significantly simplifying the protein synthesis process.
