Posttranslational modifications (PTMs) are crucial to protein function regulation. These modifications alter protein structure, activity, binding preferences, immunogenicity, aggregation, and more. Studying the exact effect of multiple PTM patterns on the biological function using libraries of synthetic peptides is essential. However, the synthesis of peptides with multiple PTM sites using solid phase peptide synthesis (SPPS) approaches is not easy. The introduction of bulky protected modified amino acids encounters difficulty in coupling which increases with the number of PTM sites. This is compensated by increasing the amount of amino acid used in SPPS, elongating the reaction time, and elevation of the reaction temperature.<br/>I will show how the recently developed strategy that combines fast overhead stirring with heating to accelerate the SPPS process became a viable way to access peptides and PTM-peptides libraries. I will demonstrate how the careful design of the reactor, which improved mass and heat transfer while keeping beads intact, allowed us to complete solid phase reactions in seconds with extreme efficiency. I will highlight how well-designed synthetic modification to the process enabled tailoring the accelerated strategy to the characteristics of each type of PTM. This study adds to the toolbox of PTM synthesis an accelerated procedure and will propel many studies that are currently hampered by state-of-the-art synthetic approaches.

Accelerated solid-phase synthesis of post-translationally modified peptides

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