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A chiroselective peptide replicator
Abstract
The origin of homochirality in living systems is often attributed to the generation of enantiomeric differences in a pool of chiral prebiotic molecules, but none of the possible physiochemical processes considered can produce the significant imbalance required if homochiral biopolymers are to result from simple coupling of suitable precursor molecules. This implies a central role either for additional processes that can selectively amplify an initially minute enantiomeric difference in the starting material, or for a nonenzymatic process by which biopolymers undergo chiroselective molecular replication. Given that molecular self-replication and the capacity for selection are necessary conditions for the emergence of life, chiroselective replication of biopolymers seems a particularly attractive process for explaining homochirality in nature. Here we report that a 32-residue peptide replicator, designed according to our earlier principles, is capable of efficiently amplifying homochiral products from a racemic mixture of peptide fragments through a chiroselective autocatalytic cycle. The chiroselective amplification process discriminates between structures possessing even single stereochemical mutations within otherwise homochiral sequences. Moreover, the system exhibits a dynamic stereochemical 'editing' function; in contrast to the previously observed error correction, it makes use of heterochiral sequences that arise through uncatalysed background reactions to catalyse the production of the homochiral product. These results support the idea that self-replicating polypeptides could have played a key role in the origin of homochirality on Earth.
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“Electrophilic and nucleophilic 16-residue peptide fragments of the same handedness were preferentially ligated, even in the presence of their enantiomers (ca.70% of diastereomeric excess was reached when peptide fragments E L , E D , N E , and N D were engaged, Fig. 21).”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [539]
In the citing paper
“The process is very sensitive to the optical purity of the substrates, fragments embedding a single (S)/(R) amino acid substitution lacked significant auto-catalytic properties.”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [539]
In the citing paper
“On the contrary, stereochemical mismatches were tolerated in the replicator; single mutated templates were able to couple homochiral fragments”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [539]
In the citing paper
“Schematic representation of the stereoselective replication of peptide residues with the same handedness.”
From Possible chemical and physical scenarios towards biological homochirality (2022) · cites this paper as [539]
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Metadata
- Authors
- Saghatelian, A., Yokobayashi, Y., Soltani, K., & Ghadiri, M. R.
- Affiliations
- Scripps Research Institute (US)
- Corresponding author
- Ghadiri, M. Reza
- Venue
- Nature
- Published
- 2001-02-15
- Volume
- 409
- Issue
- 6822
- Pages
- 797-801
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2130128712
- Cited by
- 310
- References
- 70
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 14 · 2023: 10 · 2022: 9 · 2021: 7 · 2020: 5 · 2019: 11 · 2018: 5 · 2017: 13 · 2016: 4 · 2015: 7 · 2014: 4 · 2013: 11 · 2012: 13
- FWCI
- 14.53
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- NASA Astrobiology Institute
- Topics
- Physical Sciences › Physics and Astronomy › Astronomy and Astrophysics › Origins and Evolution of Life
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Keywords
- homochirality, origin of life, autocatalysis, prebiotic chemistry
- MeSH terms
- Amino Acid Sequence, Catalysis, Molecular Sequence Data, Mutation, Peptide Fragments, Peptide Biosynthesis, Peptides, Protein Conformation, Stereoisomerism, Thermodynamics, Evolution, Chemical
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