Water-Based Dynamic Depsipeptide Chemistry: Building Block Recycling and Oligomer Distribution Control Using...

Area of Science:

• Polymer Chemistry
• Organic Chemistry
• Biochemistry

Background:

• Amide bond formation's high kinetic barrier limits reversible chemistry applications, including peptide-based dynamic libraries.
• Existing dynamic peptide chemistry strategies often require harsh conditions, catalysts, or specific functional groups.
• Depsipeptides, copolymers of amino and hydroxy acids, offer a biorelevant alternative to overcome these limitations.

Purpose of the Study:

• To explore depsipeptides as a novel system for dynamic and reversible polymer chemistry.
• To develop a model system using N-(α-hydroxyacyl)-amino acid building blocks for reversible depsipeptide formation.
• To investigate the controllable polymerization and depolymerization of depsipeptides.

Main Methods:

• Developed a model system of N-(α-hydroxyacyl)-amino acid building blocks.
• Utilized two-step evaporation-rehydration cycling under moderate conditions for polymerization.
• Exploited differential hydrolytic lifetimes of amide and ester bonds, controlled by pH, temperature, time, and side chains, for selective recycling.

Main Results:

• Demonstrated reversible polymerization of depsipeptides via dynamic ester chemistry facilitated by cyclic morpholinedione intermediates.
• Showed that polymerization and breakdown are controllable by adjusting solution conditions and building block side chains.
• Established that structural properties dictate depsipeptide half-lives and product oligomer distributions.

Conclusions:

• A cyclic, ester-based reversible depsipeptide formation mechanism was established, temporally separating polymerization and depolymerization.
• This system overcomes limitations of traditional amide-based dynamic chemistries.
• Findings have potential implications for prebiotic polymer chemical evolution and the development of new dynamic materials.