A versatile “Synthesis Tag” (SynTag) for the chemical synthesis of aggregating peptides and proteins

20 September 2023, Version 2
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

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.

Keywords

Chemical Protein Synthesis
Solid-Phase Peptide Synthesis
Difficult Sequences
Protein Tag

Supplementary materials

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