title: Thiazolidine-Masked α-Oxo Aldehyde Functionality for Peptide and Protein Modification.
abstract: α-Oxo aldehyde-based bioconjugation chemistry has been widely explored in peptide and protein modifications for various applications in biomedical research during the past decades. The generation of α-oxo aldehyde via sodium periodate oxidation is usually limited to the N-terminus of a target protein. Internal-site functionalization of proteins with the α-oxo aldehyde handle has not been achieved yet. Herein we report a novel method for site-specific peptide and protein modification using synthetically or genetically incorporated thiazolidine-protected α-oxo aldehyde. Efficient unmasking of the aldehyde was achieved by silver ion-mediated hydrolysis of thiazolidine under mild conditions for the first time. A model peptide and a recombinant protein were used to demonstrate the utility of this new method, which were site-specifically modified by oxime ligation with an oxyamine-functionalized peptide labeling reagent. Therefore, our current method has enriched the α-oxo aldehyde synthetic tool box in peptide and protein bioconjugation chemistry and holds great potential to be explored in novel applications in the future.
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: Xiaobao
authors.initials: X
authors.lastname: Bi
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: Kalyan Kumar
authors.initials: KK
authors.lastname: Pasunooti
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: Julien
authors.initials: J
authors.lastname: Lescar
authors.affiliation: School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551, Singapore.
authors.forename: Chuan-Fa
authors.identifier: 0000-0001-7433-2081
authors.initials: CF
authors.lastname: Liu
mesh_terms: D000447:Aldehydes / Q000737:chemistry*; D000595:Amino Acid Sequence; D001665:Binding Sites; D008958:Models, Molecular; D010084:Oxidation-Reduction; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*; D053778:Thiazolidines / Q000737:chemistry*
chemical_list: D000447:Aldehydes; D010455:Peptides; D011506:Proteins; D053778:Thiazolidines