Complex Molecules That Fold Like Proteins Can Emerge Spontaneously

Area of Science:

• Synthetic chemistry
• Biochemistry
• Origin of life studies

Background:

• Macromolecular folding, as seen in natural proteins, imparts diverse properties.
• Previously, complex folded molecules required either natural evolution or extensive design and synthesis.
• Autonomous formation of complex molecular architectures was not previously demonstrated.

Purpose of the Study:

• To demonstrate the autonomous and selective emergence of complex folded molecules from simple precursors.
• To identify a self-synthesizing macrocyclic foldamer with novel structural complexity.
• To establish dynamic combinatorial chemistry as a viable approach for creating complex synthetic molecules.

Main Methods:

• Dynamic combinatorial chemistry approach.
• One-step synthesis from a mixture of interconverting molecules.
• Characterization using single-crystal X-ray crystallography and Nuclear Magnetic Resonance (NMR) spectroscopy.

Main Results:

• Identification of a self-synthesizing macrocyclic foldamer constructed from 15 identical peptide-nucleobase subunits.
• Achieved a 95% yield in the folding-driven synthesis of the complex structure.
• Revealed an unprecedented secondary and tertiary structure stabilized by a network of noncovalent interactions.

Conclusions:

• Dynamic combinatorial chemistry enables the creation of synthetic molecules with folding motifs exceeding current design capabilities.
• Autonomous formation of complex folded molecules suggests a potential role in early abiogenesis.
• This work opens new avenues for designing complex molecular architectures with potential applications in various scientific fields.