Efficient and selective functionalization of peptides and proteins is essential for advancing chemical biology and therapeutic applications.In this study,we present alkynyl aldehyde as a novel thiol-specific reagent t...Efficient and selective functionalization of peptides and proteins is essential for advancing chemical biology and therapeutic applications.In this study,we present alkynyl aldehyde as a novel thiol-specific reagent that enables precise and chemoselective targeting of cysteine(Cys)residues.This approach operates in aqueous buffers under mild conditions and is broadly compatible with diverse biomolecules,ranging from small peptides to large proteins,without compromising their structural integrity or function.The incorporation of a versatile aldehyde group within the conjugates opens avenues for further functionalization,including hydrazone and oxime formation,carbon-carbon bond formation,and site-specific biotinylation.Notably,this aldehyde also facilitates proximity-driven conjugation with amine groups,enabling the formation of cyclic biomolecules.Furthermore,the method achieves remarkable stability of the conjugates under biologically relevant conditions.By providing a robust and versatile platform for protein and peptide modification,this study significantly expands the bioconjugation toolkit,offering promising applications in drug discovery,biomaterials development,and therapeutic innovation.展开更多
基金the financial support from the Distinguished University Professor grant(Nanyang Technological University),and the Agency for Science,Technology and Research(A*STAR)under its Manufacturing,Trade and Connectivity(MTC)Individual Research Grant(M21K2c0114)RIE2025 MTC Programmatic Fund(M22K9b0049).
文摘Efficient and selective functionalization of peptides and proteins is essential for advancing chemical biology and therapeutic applications.In this study,we present alkynyl aldehyde as a novel thiol-specific reagent that enables precise and chemoselective targeting of cysteine(Cys)residues.This approach operates in aqueous buffers under mild conditions and is broadly compatible with diverse biomolecules,ranging from small peptides to large proteins,without compromising their structural integrity or function.The incorporation of a versatile aldehyde group within the conjugates opens avenues for further functionalization,including hydrazone and oxime formation,carbon-carbon bond formation,and site-specific biotinylation.Notably,this aldehyde also facilitates proximity-driven conjugation with amine groups,enabling the formation of cyclic biomolecules.Furthermore,the method achieves remarkable stability of the conjugates under biologically relevant conditions.By providing a robust and versatile platform for protein and peptide modification,this study significantly expands the bioconjugation toolkit,offering promising applications in drug discovery,biomaterials development,and therapeutic innovation.
