{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T09:14:26Z","timestamp":1790154866037,"version":"4.0.1"},"reference-count":21,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2023,11,12]],"date-time":"2023-11-12T00:00:00Z","timestamp":1699747200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000879","name":"Alfred P. Sloan Foundation","doi-asserted-by":"publisher","award":["G-2021-16757"],"award-info":[{"award-number":["G-2021-16757"]}],"id":[{"id":"10.13039\/100000879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000879","name":"Alfred P. Sloan Foundation","doi-asserted-by":"publisher","award":["80NSSC20K0610"],"award-info":[{"award-number":["80NSSC20K0610"]}],"id":[{"id":"10.13039\/100000879","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000104","name":"NASA Astrobiology Program","doi-asserted-by":"publisher","award":["G-2021-16757"],"award-info":[{"award-number":["G-2021-16757"]}],"id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000104","name":"NASA Astrobiology Program","doi-asserted-by":"publisher","award":["80NSSC20K0610"],"award-info":[{"award-number":["80NSSC20K0610"]}],"id":[{"id":"10.13039\/100000104","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Life"],"abstract":"<jats:p>Most contemporary theories for the chemical origins of life include the prebiotic synthesis of informational polymers, including strong interpretations of the RNA World hypothesis. Existing challenges to the prebiotic emergence of RNA have encouraged exploration of the possibility that RNA was preceded by an ancestral informational polymer, or proto-RNA, that formed more easily on the early Earth. We have proposed that the proto-nucleobases of proto-RNA would have readily formed glycosides with ribose and that these proto-nucleosides would have formed base pairs as monomers in aqueous solution, two properties not exhibited by the extant nucleosides or nucleotides. Here we demonstrate that putative proto-nucleotides of the model proto-nucleobases barbituric acid and melamine can be formed in the same one-pot reaction with ribose-5-phosphate. Additionally, the proto-nucleotides formed in these reactions spontaneously form assemblies that are consistent with the presence of Watson\u2013Crick-like base pairs. Together, these results provide further support for the possibility that heterocycles closely related to the extant bases of RNA facilitated the prebiotic emergence of RNA-like molecules, which were eventually replaced by RNA over the course of chemical and biological evolution.<\/jats:p>","DOI":"10.3390\/life13112200","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:10:43Z","timestamp":1699841443000},"page":"2200","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["One-Pot Formation of Pairing Proto-RNA Nucleotides and Their Supramolecular Assemblies"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1206-3239","authenticated-orcid":false,"given":"Tyler P.","family":"Roche","sequence":"first","affiliation":[{"name":"School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pranav J.","family":"Nedumpurath","sequence":"additional","affiliation":[{"name":"School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suneesh C.","family":"Karunakaran","sequence":"additional","affiliation":[{"name":"School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary B.","family":"Schuster","sequence":"additional","affiliation":[{"name":"School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas V.","family":"Hud","sequence":"additional","affiliation":[{"name":"School of Chemistry & Biochemistry, Georgia Institute of Technology, Atlanta, GA 30332, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,12]]},"reference":[{"key":"ref_1","unstructured":"Gesteland, R.F., Cech, T.R., and Atkins, J.F. (2006). The RNA World, Cold Spring Harbor Laboratory Press. [3rd ed.]."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/319618a0","article-title":"The RNA World","volume":"319","author":"Walter","year":"1986","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1089\/ast.2012.0868","article-title":"The \u201cstrong\u201d RNA world hypothesis: Fifty years old","volume":"13","author":"Neveu","year":"2013","journal-title":"Astrobiology"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"4766","DOI":"10.1021\/acs.chemrev.9b00546","article-title":"The chemistry of abiotic nucleotide synthesis","volume":"120","author":"Yadav","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1126\/science.aax2747","article-title":"Unified prebiotically plausible synthesis of pyrimidine and purine RNA ribonucleotides","volume":"366","author":"Becker","year":"2019","journal-title":"Science"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Engelhart, A.E., and Hud, N.V. (2010). Primitive genetic polymers. Cold Spring Harb. Perspect. Biol., 2.","DOI":"10.1101\/cshperspect.a002196"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"466","DOI":"10.1016\/j.chembiol.2013.03.012","article-title":"The origin of RNA and \u2018My Grandfather\u2019s Axe\u2019","volume":"20","author":"Hud","year":"2013","journal-title":"Chem. Biol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1021\/acs.chemrev.0c00069","article-title":"Prebiotic syntheses of noncanonical nucleosides and nucleotides","volume":"120","author":"Fialho","year":"2020","journal-title":"Chem. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"12412","DOI":"10.1002\/anie.201103672","article-title":"Etiology of potentially primordial biomolecular structures: From vitamin B12 to the nucleic acids and an inquiry into the chemistry of life\u2019s origin: A retrospective","volume":"50","author":"Eschenmoser","year":"2011","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"884","DOI":"10.1126\/science.aat0971","article-title":"Hachimoji DNA and RNA: A genetic system with eight building blocks","volume":"363","author":"Hoshika","year":"2019","journal-title":"Science"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"9279","DOI":"10.1021\/jacs.0c13081","article-title":"Water-soluble supramolecular polymers of paired and stacked heterocycles: Assembly, structure, properties, and a possible path to pre-RNA","volume":"143","author":"Schuster","year":"2021","journal-title":"J. Am. Chem. Soc."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"5640","DOI":"10.1021\/ja410124v","article-title":"Spontaneous prebiotic formation of a \u03b2-ribofuranoside that self-assembles with a complementary heterocycle","volume":"136","author":"Chen","year":"2014","journal-title":"J. Am. Chem. Soc."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"11328","DOI":"10.1038\/ncomms11328","article-title":"Spontaneous formation and base pairing of plausible prebiotic nucleotides in water","volume":"7","author":"Cafferty","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1263","DOI":"10.1039\/C7OB03017G","article-title":"Glycosylation of a model proto-RNA nucleobase with non-ribose sugars: Implications for the prebiotic synthesis of nucleosides","volume":"16","author":"Fialho","year":"2018","journal-title":"Org. Biomol. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e202203036","DOI":"10.1002\/chem.202203036","article-title":"A Plausible Prebiotic Path to Nucleosides: Ribosides and Related Aldosides Generated from Ribulose, Fructose, and Similar Abiotic Precursors","volume":"29","author":"Roche","year":"2022","journal-title":"Chem. Eur. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"4411","DOI":"10.1002\/chem.200802656","article-title":"Synthesis of pyrimidines and triazines in ice: Implications for the prebiotic chemistry of nucleobases","volume":"15","author":"Guzman","year":"2009","journal-title":"Chem. Eur. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/0371-1951(64)80037-0","article-title":"Absorption spectra of solutions of cyanuric acid and its chlorinated derivatives","volume":"20","author":"Sancier","year":"1964","journal-title":"Spectrochim. Acta"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Ortiz-Rodr\u00edguez, L.A., Hoehn, S.J., and Crespo-Hern\u00e1ndez, C.E. (2022). On the Photostability of Cyanuric Acid and Its Candidature as a Prebiotic Nucleobase. Molecules, 27.","DOI":"10.3390\/molecules27041184"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1021\/ar00049a006","article-title":"Noncovalent synthesis: Using physical-organic chemistry to make aggregates","volume":"28","author":"Whitesides","year":"1995","journal-title":"Acc. Chem. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1002\/bscb.19520610105","article-title":"Absorption Spectra and Structure of Barbituric Acid Derivatives as a Function of pH","volume":"61","author":"Fox","year":"1952","journal-title":"Bull. Soc. Chim. Belg."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"6079","DOI":"10.1021\/jacs.0c12010","article-title":"X-ray Fiber Diffraction and Computational Analyses of Stacked Hexads in Supramolecular Polymers: Insight into Self-Assembly in Water by Prospective Prebiotic Nucleobases","volume":"143","author":"Alenaizan","year":"2021","journal-title":"J. Am. Chem. Soc."}],"container-title":["Life"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/11\/2200\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:21:46Z","timestamp":1760131306000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-1729\/13\/11\/2200"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,11,12]]},"references-count":21,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2023,11]]}},"alternative-id":["life13112200"],"URL":"https:\/\/doi.org\/10.3390\/life13112200","relation":{},"ISSN":["2075-1729"],"issn-type":[{"value":"2075-1729","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,11,12]]}}}