Spontaneous Peptide Ligation Mediated by Cysteamine.

Area of Science:

• Astrobiology
• Organic Chemistry
• Biochemistry

Background:

• Peptides are fundamental to life, suggesting a crucial role in abiogenesis.
• Spontaneous, chemoselective peptide synthesis in water is a key unsolved problem in origin of life research.
• Aminonitriles are considered prebiotic precursors but do not readily polymerize in water.

Purpose of the Study:

• To investigate the potential of prebiotically plausible molecules for spontaneous peptide synthesis in water.
• To identify a catalyst or precursor that enables efficient and selective peptide bond formation under early Earth conditions.

Main Methods:

• Utilized cysteamine, a prebiotically plausible aminothiol, in Strecker chemistry reactions.
• Investigated the polymerization of resulting β-mercaptoethyl-α-aminonitriles and β-mercaptoethyl-amino acids in aqueous conditions.
• Analyzed the kinetics, yield, and selectivity of the intramolecular thiol-catalyzed ligation process.

Main Results:

• Demonstrated that cysteamine yields β-mercaptoethyl-α-aminonitriles and amino acids that spontaneously form peptides in water.
• Showcased intramolecular thiol-catalyzed ligation as a faster, higher-yielding, and more α-selective method than previous prebiotic chemistries.
• Achieved highly regioselective α-ligation of specific dinitriles in quantitative yields.

Conclusions:

• Cysteamine can facilitate the selective chemical synthesis of prebiotic α-peptides in water.
• The findings suggest cysteamine, a component of coenzyme A, may have been vital for early peptide formation.
• This work provides a plausible chemical pathway for the synthesis of peptides, crucial building blocks of life.