Submonomer synthesis of sequence defined peptoids with diverse side-chains

Area of Science:

• Polymer Science
• Biomedicine
• Nanoscience

Background:

• Peptoids are sequence-defined oligomers of N-substituted glycine monomers.
• Solid-phase submonomer synthesis provides efficient access to a diverse range of peptoid sequences.
• The versatility of peptoid chemistry allows for custom design in various scientific fields.

Purpose of the Study:

• To provide detailed, optimized protocols for peptoid synthesis.
• To make peptoid synthesis accessible to researchers without extensive chemistry backgrounds.
• To detail methods for incorporating diverse side chains and creating hybrid structures.

Main Methods:

• Solid-phase submonomer synthesis compatible with Fmoc-peptide chemistry.
• Automation on existing peptide synthesizers using provided protocols.
• Specific methods for incorporating amino-acid-like and non-natural side chains.

Main Results:

• Optimized protocols for peptoid synthesis are presented.
• The synthesis method is compatible with automated peptide synthesizers.
• Methods for creating peptoid conjugates and peptide-peptoid hybrids are included.

Conclusions:

• Peptoid synthesis is readily achievable with optimized protocols, even for non-chemists.
• The submonomer method allows for extensive exploration of peptoid sequence space.
• This work facilitates the application of custom-designed peptoids across multiple disciplines.