N‐Phenyl‐N‐aceto‐vinylsulfonamides as Efficient and Chemoselective Handles for N‐Terminal Modification of Peptides and Proteins

Publisher： John Wiley & Sons Inc

E-ISSN： 1099-0690|2018|6|829-836

ISSN： 1434-193x

Source： EUROPEAN JOURNAL OF ORGANIC CHEMISTRY, Vol.2018, Iss.6, 2018-02, pp. : 829-836

Disclaimer: Any content in publications that violate the sovereignty, the constitution or regulations of the PRC is not accepted or approved by CNPIEC.

Previous Menu Next

Abstract

A number of vinylsulfonamides were synthesized and screened to identify reagents that can be used to modify octreotide under biological pH and room temperature with improved efficiency. N‐Phenyl‐N‐aceto‐vinylsulfonamide exhibits higher reactivity and has emerged as an efficient reagent that has the ability to realize the selective modification of peptides and proteins at the N‐terminus via aza‐Michael addition. We showed that, after conjugation of peptides and proteins with the reagent containing a bioorthogonal functional group, the derivatives could be further labelled by functionalities, including fluorescent tags, modified drugs and polyethylene glycol (PEG) polymers without the need for prior treatment. Somatostatin, lysozyme, and RNaseA were selectively modified at the N‐terminus, which illustrated the application of the method.