Sequence-Specific β-Peptide Synthesis by a Rotaxane-Based Molecular Machine

Area of Science:

• Molecular Machines
• Synthetic Chemistry
• Biotechnology

Background:

• Ribosomes typically synthesize peptides using proteinogenic amino acids.
• Nonproteinogenic amino acids, such as β³-amino acids, are challenging for ribosomal synthesis, especially consecutively.
• Artificial molecular machines offer novel pathways for peptide synthesis.

Purpose of the Study:

• To report the synthesis and operation of a rotaxane-based artificial molecular machine.
• To demonstrate sequence-specific synthesis of β-homo (β³) peptides.
• To explore the capability of artificial machines in handling challenging ligation transition states.

Main Methods:

• Synthesis of a three-barrier, rotaxane-based artificial molecular machine.
• Utilizing nonproteinogenic β³-amino acids for peptide synthesis.
• Employing native chemical ligation (NCL) for peptide bond formation.
• Demonstrating the removal of the catalyst region by peptidases.

Main Results:

• Successful synthesis and operation of the artificial molecular machine.
• Sequence-specific synthesis of β-homo (β³) peptides.
• Demonstration of successful ligation for 15- and 19-membered transition states.
• Generation of a unique peptide product through the combined action of artificial and biological machines.

Conclusions:

• Artificial molecular machines can perform sequence-specific synthesis of β-homo (β³) peptides.
• Challenging ligation transition states are compatible with information translation by this artificial machine.
• The integration of artificial and biological machines enables the creation of peptides unattainable by either system independently.