Sequence-Selective Decapeptide Synthesis by the Parallel Operation of Two Artificial Molecular Machines

Area of Science:

• Supramolecular Chemistry
• Synthetic Chemistry
• Biotechnology

Background:

• Molecular machines offer precise control over chemical synthesis.
• Complex peptide synthesis remains a challenge for traditional methods.
• Mimicking biological processes can inspire novel synthetic strategies.

Purpose of the Study:

• To synthesize a decapeptide using two parallel rotaxane-based molecular machines.
• To demonstrate a novel approach to complex peptide assembly.
• To explore the potential of molecular machines in mimicking biological post-translational modifications.

Main Methods:

• Simultaneous operation of two molecular peptide synthesizers in one vessel.
• Selective residue activation and directional ligation of intermediates.
• Utilizing a thioproline to cysteine transformation and a macrocycle-peptide hydrazine linkage.
• Employing a Glu residue for product release and machinery removal.

Main Results:

• Successful preparation of a decapeptide through a four-stage process.
• Demonstrated selective transformation of thioproline to cysteine within a hexapeptide intermediate.
• Achieved directional ligation of intermediates via a macrocycle-peptide hydrazine linkage.
• Enabled simultaneous product release and assembly machinery removal using a Glu residue.

Conclusions:

• Rotaxane-based molecular machines can be operated in parallel for complex decapeptide synthesis.
• The developed system mimics biological ligation and post-translational modification.
• This approach expands the capabilities of molecular machines for synthesizing challenging biomolecules.