A hydrophobic disordered peptide spontaneously anchors a covalently bound RNA hairpin to giant lipidic vesicles

Isaad, Alexandra Le Chevalier; Carrara, Paolo; Stano, Pasquale; Krishnakumar, Kollappillil S.; Lafont, Dominique; Zamboulis, Alexandra; Buchet, René; Bouchu, Denis; Albrieux, Florian; Strazewski, Peter

doi:10.1039/c4ob00721b

Cited by 13 publications

(6 citation statements)

References 68 publications

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“…1 H NMR (300 MHz, CDCl 3 ) δ ppm 7.29 (m, 18H), 7.18 (m, 2H), 5.02–4.25 (m, 10H), 4.09 (m, 2H), 3.84 (dd, J=5.99, 8.28, 1H), 3.71 (m, 2H), 3.62 (m, 3H), 3.46 (t, J=7.93, 2H), 1.42 (s, 3H), 1.37 (s, 3H). Spectral data is consistent with the literature [57a] …”

Section: Methodssupporting

confidence: 91%

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

et al. 2022

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Invariant natural killer (iNK) T cells, Type I iNKTs, are responsible for the production of pro‐inflammatory cytokines which induce a systemic immune response. They are distinctive in possessing an semi‐invariant T‐cell receptor that recognizes glycolipid antigens presented by CD1d, a protein closely related to the class I major histocompatibility complex, conserved across multiple mammalian species in a class of proteins well‐renowned for their high degree of polymorphism. This receptor's first potent identified antigen is the α‐galactosylceramide, KRN7000, a synthetic glycosphingolipid closely related to those isolated from bacteria that were found on a Japanese marine sponge. A corresponding terrestrial antigen remained unidentified until two specific diacylglycerol‐containing glycolipids, reported to activate iNKT cells, were isolated from Streptococcus pneumoniae. We report the total synthesis and immunological re‐evaluation of these two glycolipids. The compounds are unable to meaningfully activate iNKT cells. Computational modelling shows that these ligands, while being capable of interacting with the CD1d receptor, create a different surface for the binary complex that makes formation of the ternary complex with the iNKT T‐cell receptor difficult. Together these results suggest that the reported activity might have been due to an impurity in the original isolated sample and highlights the importance of taking care when reporting biological activity from isolated natural products.

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Section: Methodssupporting

confidence: 91%

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

et al. 2022

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“…Further,l ipophilic peptidyl chains may have anchored peptidyl RNAs on amembrane,retaining it in aprotocell. [38] Further,specific RNAsequences of peptidyl RNAs may have templated peptide growth or vice versa, and intramolecular interactions during chain growth (that are entropically favored over intermolecular interactions) may have led to the emergence of af irst genetic code. [19] If so,o ur findings support Eigens proposal of primitive "tRNAs" as the earliest components of the translational machinery.…”

Section: Methodsmentioning

confidence: 99%

“…Strands complementary to the RNA portion of the peptidyl RNA may have stabilized it against degradation, and may have eventually become precursors of today’s mRNAs. Further, lipophilic peptidyl chains may have anchored peptidyl RNAs on a membrane, retaining it in a protocell 38. Further, specific RNA sequences of peptidyl RNAs may have templated peptide growth or vice versa, and intramolecular interactions during chain growth (that are entropically favored over intermolecular interactions) may have led to the emergence of a first genetic code 19.…”

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confidence: 99%

Spontaneous Formation of RNA Strands, Peptidyl RNA, and Cofactors

2015

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How the biochemical machinery evolved from simple precursors is an open question. Here we show that ribonucleotides and amino acids condense to peptidyl RNAs in the absence of enzymes under conditions established for genetic copying. Untemplated formation of RNA strands that can encode genetic information, formation of peptidyl chains linked to RNA, and formation of the cofactors NAD+, FAD, and ATP all occur under the same conditions. In the peptidyl RNAs, the peptide chains are phosphoramidate-linked to a ribonucleotide. Peptidyl RNAs with long peptide chains were selected from an initial pool when a lipophilic phase simulating the interior of membranes was offered, and free peptides were released upon acidification. Our results show that key molecules of genetics, catalysis, and metabolism can emerge under the same conditions, without a mineral surface, without an enzyme, and without the need for chemical pre-activation.

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“…Additionally, it is important to consider that the lipid environment that we used provides a two dimensional constraint to the mobility of the starting reactants [6], facilitating increased local concentration and favoring energetically uphill reaction like the oligomerization of nucleotides. Furthermore, once the RNA is formed, lipids can encapsulate it within vesicles, a process that is favored by the presence of other molecules such as hydrophobic peptides [7], similar to what is thought to have occurred on the early Earth.…”

Section: Synthesis Of Nucleic Acids In a Lipid Mediummentioning

confidence: 96%

Lipid-Assisted Polymerization of Nucleotides

Olasagasti

Rajamani

2019

Life

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In addition to being one of the proponents of the “Lipid World hypothesis”, David Deamer, together with other colleagues, pioneered studies involving formation of RNA-like oligomers from their ‘non-activated’, prebiotically plausible monomeric moieties. In particular, the pioneering work in this regard was a publication from 2008 in Origins of Life and Evolution of Biospheres, The Journal of the International Astrobiology Society, wherein we described the formation of RNA-like oligomers from nucleoside 5’-monophosphates. In that study, we had simulated a terrestrial geothermal environment, a niche that is thought to have facilitated the prebiotic non-enzymatic synthesis of polynucleotides. We showed that a mixture of lipids and non-activated mononucleotides resulted in the formation of relatively long strands of RNA-like polymers when subjected to repeated cycles of dehydration and rehydration (DH-RH). Since 2008, terrestrial geothermal niches and DH-RH conditions have been explored in the context of several other prebiotic processes. In this article, we review the work that we and other researchers have carried out since then in this line of research, including the development of new apparatus to carry out the simulation of prebiotic terrestrial geothermal environments.

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A hydrophobic disordered peptide spontaneously anchors a covalently bound RNA hairpin to giant lipidic vesicles

Cited by 13 publications

References 68 publications

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

The Total Synthesis of Glycolipids from Streptococcus pneumoniae and a Re‐evaluation of Their Immunological Activity**

Spontaneous Formation of RNA Strands, Peptidyl RNA, and Cofactors

Lipid-Assisted Polymerization of Nucleotides

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