A sulfonium tethered peptide ligand rapidly and selectively modifies protein cysteine in vicinity.

ABSTRACT: Significant efforts have been invested to develop site-specific protein modification methodologies in the past two decades. In most cases, a reactive moiety was installed onto ligands with the sole purpose of reacting with specific residues in proteins. Herein, we report a unique peptide macrocyclization method via the bis-alkylation between methionine and cysteine to generate cyclic peptides with significantly enhanced stability and cellular uptake. Notably, when the cyclized peptide ligand selectively recognizes its protein target with a proximate cysteine, a rapid nucleophilic substitution could occur between the protein Cys and the sulfonium center on the peptide to form a conjugate. The conjugation reaction is rapid, facile and selective, triggered solely by proximity. The high

SUBMITTER: Wang D 

PROVIDER: S-EPMC6530539 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature