2023/09/20 by H Burgisser, Elyse T. Williams, Robin Lescure +3 · 1 voice
Biochemistry, Genetics and Molecular Biology · Chemistry · Immunology and Microbiology · #Chemical Synthesis and Analysis #Click Chemistry and Applications #Antimicrobial Peptides and Activities
paper · pdf · doi:10.26434/chemrxiv-2023-7mz2c-v2
openalex publication_date 2023/09/20 · openalex created_date 2025/10/10 · openalex updated_date 2026/08/01
Solid-phase peptide synthesis (SPPS) and native chemical ligation (NCL) are powerful methods for obtaining peptides and proteins that are otherwise inaccessible. Nonetheless, numerous sequences are difficult to prepare via SPPS, and cleaved peptides often have low aqueous solubility. To address these challenges, we developed a “Synthesis Tag” consisting of six arginines connected via a cleavable MeDbz linker. “SynTag” effectively improves batch- and flow-SPPS of “difficult sequences”, enhances solubility of the cleaved peptides and provides direct access to native sequences by hydrolysis, or peptide thioesters for NCL. We demonstrate its utility in the first chemical synthesis of the MYC transactivation domain with a single NCL. We envisage SynTag to become a broadly applicable tool that enables the synthesis and study of previously unattainable peptides and proteins.