Origin & Evolution of Life

From the RNA-Peptide World: Prebiotic Reaction Conditions Compatible with Lipid Membranes for the Formation of Lipophilic Random Peptides in the Presence of Short Oligonucleotides, and More

By Keith Cowing
Status Report
Life
January 29, 2024
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From the RNA-Peptide World: Prebiotic Reaction Conditions Compatible with Lipid Membranes for the Formation of Lipophilic Random Peptides in the Presence of Short Oligonucleotides, and More
Work plan: RNA oligomers (upper left box, also DNA and DNA-RNA hybrid constructs) for their ligation (upper right box, also untemplated elongation) and their peptidylation with relatively lipophilic peptide mixtures (lower left box) to give amphiphilic peptide–oligonucleotide chimeras (lower right box) outside or inside the lumen of mixed-lipid giant vesicles (GVs). A = adenylate (or 2′-deoxyadenylate), G = guanylate (or 2′-deoxyguanylate), C = uridylate, T = thymidylate, Fluo = fluorophore, P = terminal phosphate, OH = terminal hydroxy group, EDC = 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, CDI = N,N’-carbonyldiimidazole, ImH = imidazole, R = H (Gly), CH3 (Ala), isopropyl (Val), isobutyl (Leu), CH2OPO3H2 (phosphoserine), CH2N3 (β-azido-alanine). — Life

Deciphering the origins of life on a molecular level includes unravelling the numerous interactions that could occur between the most important biomolecules being the lipids, peptides and nucleotides. They were likely all present on the early Earth and all necessary for the emergence of cellular life.

In this study, we intended to explore conditions that were at the same time conducive to chemical reactions critical for the origins of life (peptide–oligonucleotide couplings and templated ligation of oligonucleotides) and compatible with the presence of prebiotic lipid vesicles.

For that, random peptides were generated from activated amino acids and analysed using NMR and MS, whereas short oligonucleotides were produced through solid-support synthesis, manually deprotected and purified using HPLC. After chemical activation in prebiotic conditions, the resulting mixtures were analysed using LC-MS. Vesicles could be produced through gentle hydration in similar conditions and observed using epifluorescence microscopy.

Despite the absence of coupling or ligation, our results help to pave the way for future investigations on the origins of life that may gather all three types of biomolecules rather than studying them separately, as it is still too often the case.

From the RNA-Peptide World: Prebiotic Reaction Conditions Compatible with Lipid Membranes for the Formation of Lipophilic Random Peptides in the Presence of Short Oligonucleotides, and More
Augustin Lopez, Antoine Vauchez, Ghinwa Ajram, Anastasiia Shvetsova, Gabrielle Leveau, Michele Fiore and Peter Strazewski
Life 2024, 14(1), 108; DOI: 10.3390/life14010108
https://www.mdpi.com/2075-1729/14/1/108
astrobiology

Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp veteran, (he/him) 🖖🏻