Stereoselective Carbene Transfer and Cascade Activity by Short-Peptide-Based Cross-β Amyloids

Area of Science:

• Biochemistry and Chemical Biology
• Catalysis and Reaction Engineering
• Origin of Life and Astrobiology

Background:

• Enzymes, utilizing specific cofactors, are crucial for stereoselective chemical transformations in biological systems.
• The structural basis for stereoselective catalysis in early protein folds remains largely unexplored.
• Understanding primitive catalytic mechanisms is key to deciphering early life processes.

Purpose of the Study:

• To investigate the catalytic capabilities of short-peptide-based amyloids in conjunction with hemin.
• To explore the stereoselective carbene transfer reactions facilitated by these minimalistic catalytic systems.
• To examine the potential for these systems to mimic enzymatic activity and regulate their own assembly.

Main Methods:

• Synthesis and characterization of short peptide-based amyloid structures.
• Complexation of peptide assemblies with hemin as a cofactor.
• Assay development for monitoring carbene transfer reactions and subsequent hydrolysis under equilibrium and non-equilibrium conditions.

Main Results:

• Short peptide-amyloid-hemin complexes demonstrated significant stereoselectivity in carbene transfer reactions, specifically cyclopropanation.
• The catalytic system exhibited hydrolase activity, degrading the cyclopropanation product.
• A cyclopropanation-hydrolysis cascade reaction was observed, providing negative feedback to the amyloid assembly process.

Conclusions:

• Short peptide-based assemblies with hemin serve as minimalistic yet potent catalytic systems for complex chemical transformations.
• These systems display remarkable catalytic diversity and stereoselectivity, mimicking aspects of enzymatic function.
• The findings open avenues for designing novel catalytic methodologies with broad applications, inspired by early biological catalysts.