Strategies for late-stage modification of peptides play a vital role in bioconjugation chemistry.Herein,a mild and site-specific copper-catalyzed late-stage peptide modification strategy is realized by leveraging a ph...Strategies for late-stage modification of peptides play a vital role in bioconjugation chemistry.Herein,a mild and site-specific copper-catalyzed late-stage peptide modification strategy is realized by leveraging a phenylalanine-based boronic acid“handle”and intra-or intermolecular imidazole derivatives.The unique selectivity for the imidazole component over unprotected amino acid side chains characterizes its great functional group tolerance and broad substrate scope.Additionally,it offers robust flexibility and structural diversity,enabling the incorporation of drug-relevant and biological molecules to furnish peptide-drug conjugates as well as cyclic peptides,which is leveraged by manipulation of an easily prepared histidine linkage.This protocol may hold significant potential for the development of peptidic and peptidomimetic drugs.展开更多
基金the financial support from the Key Project of Science and Technology Innovation 2030(grant no.2023ZD0121002)the Startup Funding of Zhejiang University,and the Huahai Young Scholars Scientific Research Innovation Foundation at the School of Pharmacy,Zhejiang University。
文摘Strategies for late-stage modification of peptides play a vital role in bioconjugation chemistry.Herein,a mild and site-specific copper-catalyzed late-stage peptide modification strategy is realized by leveraging a phenylalanine-based boronic acid“handle”and intra-or intermolecular imidazole derivatives.The unique selectivity for the imidazole component over unprotected amino acid side chains characterizes its great functional group tolerance and broad substrate scope.Additionally,it offers robust flexibility and structural diversity,enabling the incorporation of drug-relevant and biological molecules to furnish peptide-drug conjugates as well as cyclic peptides,which is leveraged by manipulation of an easily prepared histidine linkage.This protocol may hold significant potential for the development of peptidic and peptidomimetic drugs.
