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Updated: Jun 16, 2025

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Published on: September 16, 2019
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Stereoselectivity of Aminoacyl-RNA Loop-Closing Ligation
Shannon Kim1, Marco Todisco1, Aleksandar Radakovic1
1Howard Hughes Medical Institute, Department of Chemistry, University of Chicago, Chicago, Illinois 60637, United States.
Journal of the American Chemical Society
|May 29, 2025
Summary
The origin of life
Area of Science:
- Origin of Life Studies
- Biochemistry
- RNA World Hypothesis
Background:
- Amino acid homochirality is a fundamental question in the origin of life.
- Enantiopure nucleotides are essential for nonenzymatic RNA replication, suggesting early nucleotide homochirality.
- The mechanism by which homochiral RNA influenced other biomolecules, like amino acids, remains unclear.
Purpose of the Study:
- To investigate if and how homochiral RNA can impose homochirality on amino acids.
- To explore aminoacyl-RNA loop-closing ligation as a mechanism for stereoselective amino acid incorporation.
- To understand the role of RNA in the selection of L-amino acids.
Main Methods:
- Examined aminoacyl-RNA loop-closing ligation reactions.
- Compared reaction rates for L-amino acids versus D-amino acids.
- Identified specific RNA sequences for selective amino acid capture.
- Investigated stereoselectivity in ligation products.
Main Results:
- Aminoacyl-RNA loop-closing ligation proceeds significantly faster with L-amino acids than D-amino acids.
- A specific RNA sequence was found to almost exclusively capture L-amino acids.
- Ligation of aminoacyl-L-RNA demonstrated inverse stereoselectivity, favoring D-amino acids.
Conclusions:
- RNA can act as a stereoselective template, influencing amino acid chirality.
- This process likely played a role in the selection of L-amino acids.
- This mechanism provides a pathway for the evolution of homochiral peptides and proteins.
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