Prebiotic Synthesis of Cysteine Peptides That Catalyze Peptide Ligation in Neutral Water. Foden, C., Islam, S., Fernandez Garcia, C. A., Maugeri, L., Sheppard, T., & Powner, M. Science, 370(6518):865–869, 2020. ![Prebiotic Synthesis of Cysteine Peptides That Catalyze Peptide Ligation in Neutral Water [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 4 downloads Peptides and the proteinogenic $α$-amino acids are essential to all life on Earth. Peptide biosynthesis is orchestrated by a complex suite of enzymes in extant biology, but this must have been predated by a simple chemical synthesis at the origins of life. $α$-Aminonitriles, the nitrile precursors of $α$-amino acids, are generally readily produced by Strecker reactions, but the origin of cysteine-the thiol-bearing amino acid-is not understood. The aminothiol moiety of cysteine is chemically incompatible with nitriles at physiological pH, therefore cysteine nitrile is not stable, and it is widely believed that cysteine was a biological invention and a late addition to the genetic code. Here, we report the first high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic synthesis converts serine to cysteine, bypassing the Strecker reaction of $β$-mercaptoacetaldehyde, but exploits nitrile-activated dehydroalanine synthesis at near-neutral pH. We additionally demonstrate the catalytic prowess of N-acylcysteines (and related peptides and thiols) in the organocatalytic synthesis of peptides and peptidyl amidines in neutral water. Thiol catalysis directly couples kinetically stable-but energy-rich-$α$-amidonitriles to proteinogenic amines, in a reaction that tolerates all twenty proteinogenic side chains. This is a rare, prebiotically plausible example of selective and efficient organocatalysis in water. Our results implicate cysteine derivatives and thiol-catalysis at the onset of evolution.
@article{Foden2020,
abstract = {Peptides and the proteinogenic $\alpha$-amino acids are essential to all life on Earth. Peptide biosynthesis is orchestrated by a complex suite of enzymes in extant biology, but this must have been predated by a simple chemical synthesis at the origins of life. $\alpha$-Aminonitriles, the nitrile precursors of $\alpha$-amino acids, are generally readily produced by Strecker reactions, but the origin of cysteine-the thiol-bearing amino acid-is not understood. The aminothiol moiety of cysteine is chemically incompatible with nitriles at physiological pH, therefore cysteine nitrile is not stable, and it is widely believed that cysteine was a biological invention and a late addition to the genetic code. Here, we report the first high-yielding, prebiotic synthesis of cysteine peptides. Our biomimetic synthesis converts serine to cysteine, bypassing the Strecker reaction of $\beta$-mercaptoacetaldehyde, but exploits nitrile-activated dehydroalanine synthesis at near-neutral pH. We additionally demonstrate the catalytic prowess of N-acylcysteines (and related peptides and thiols) in the organocatalytic synthesis of peptides and peptidyl amidines in neutral water. Thiol catalysis directly couples kinetically stable-but energy-rich-$\alpha$-amidonitriles to proteinogenic amines, in a reaction that tolerates all twenty proteinogenic side chains. This is a rare, prebiotically plausible example of selective and efficient organocatalysis in water. Our results implicate cysteine derivatives and thiol-catalysis at the onset of evolution.},
author = {Foden, Callum and Islam, Saidul and {Fernandez Garcia}, Christian Arturo and Maugeri, Leonardo and Sheppard, Tom and Powner, Matthew},
doi = {10.1126/science.abd5680},
file = {:C$\backslash$:/Users/Benji/Downloads/865.full.pdf:pdf},
journal = {Science},
keywords = {biomimetic chemistry,cysteine side chains,organocatalysis,origins of life,peptide ligation},
number = {6518},
pages = {865--869},
title = {{Prebiotic Synthesis of Cysteine Peptides That Catalyze Peptide Ligation in Neutral Water}},
url = {https://science.sciencemag.org/content/370/6518/865},
volume = {370},
year = {2020}
}
Downloads: 4
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