Membranes Composed of Lipopeptides and Liponucleobases Inspired Protolife Evolution


Amino acids and peptides have been demonstrated to form lipoamino acids and lipopeptides under presumed prebiotic conditions, and readily form liposomes. Of the common nucleobases, adenine forms a liponucleobase even below 100 °C. Adenine as well as other nucleobases can also be derivatized with ethylene carbonate (and likely other similar compounds) onto which fatty acids can be attached. The fatty acid tails along with appropriately functionalized nucleobases provide some solubility of liponucleobases in membranes. Such membranes would provide a structure in which three of biology’s major components are closely associated and available for chemical interactions. Nucleobase-to-nucleobase interactions would ensure that the liponucleobases would have a uniquely different head-group relationship than other amphiphiles within a membrane, likely forming rafts due their π-π interactions and providing surface discontinuities that could serve as catalytic sites. The π-π bond distance in aromatic compounds is typically 0.34 nm, commensurate with that of the amine to carboxylate distance in alpha amino acids. This would have provided opportunity for hydrogen bonding between amino acids and the distal primary amines or tautomeric carbonyl/hydroxyl groups of two π-bonded nucleobases. Such bonding would weaken the covalent linkages within the amino acids, making them susceptible to forming peptide bonds with an adjacent amino acid, likely a lipoamino acid or lipopeptide. Were this second lipoamino acid bound to a third π-bonded nucleobase, it could result in orientation, destabilization and peptide formation. The stacked triplet of nucleobases might constitute the primordial codon triplet from which peptides were synthesized: primordial translation.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2


  1. Arnold K, Davies B, Richard L, Giles RL, Grosjean C, Smith GE, Whiting A (2006) To catalyze or not to catalyze? Insight into direct amide bond formation from amines and carboxylic acids under thermal and catalyzed conditions. Adv Synth Catal 348:813–820

  2. Bernal JD (1924) The structure of graphite. Proc Royal Soc London A 106(740):749–773

  3. Black RA, Blosser MC (2016) A self-assembled aggregate composed of a fatty acid membrane and the building blocks of biological polymers provides a first step in the emergence of protocells. Life 6:33–48

  4. Black RA, Blosser MC, Stottrup BL, Tavakley R, Deamer DW, Keller SL (2013) Nucleobases bind to and stabilize aggregates of a prebiotic amphiphile, providing a viable mechanism for the emergence of protocells. PNAS 110(33):13272–13276

  5. Chemical “Bond strain” (n.d.) Creative enzymes, resource: bond strain. . Accessed 13 Sept 2019

  6. Bouhadir I, Abramian L, Ezzeddine A, Usher K, Vladimirov N (2012) Synthesis, cyclopolymerization and cyclo-copolymerization of 9-(2-diallylaminoethyl)adenine and its hydrochloride salt. Molecules 17:13290–13306

  7. Bugella-Altamirano E, Choquesillo-Lazarte D, González-Pérez JM, Sánchez-Moreno MJ, Marı́n-Sánchez R, Martı́n-Ramos JD, Covelo B, Carballo R, Castiñeiras A, Niclós-Gutiérrez J (2002) Three new modes of adenine-copper (II) coordination: interligand interactions controlling the selective N3-, N7- and bridging-N3,N7/metal-bonding of adenine to different N-substituted iminodiacetato-copper(II) chelates. Inorg Chim Acta 339:160–170

  8. Bullock C (2000) The archaea-a biochemical perspective. Biochem Educ 28:186–191

  9. Caetano-Anolles G, Seufferheld MJ (2013) The coevolutionary roots of biochemistry and cellular organization challenge the RNA world paradigm. J Mol Microbiol Biotechnol 23:152–177

  10. Carter WC (2016) An alternative to the RNA world. Nat Hist 125(1):28–33

  11. Corey RB (1940) Interatomic distances in proteins and related substances. Chem Rev 26(2):227–236

  12. Crick FHC (1968) The origin of the genetic code. J Mol Biol 38:367–379

  13. Cui Q, Karplus M (2008) Allostery and cooperativity revisited. Protein Sci 17(8):1295–1307

  14. Damer B, Deamer D (2015) Coupled phases and combinatorial selection in fluctuating hydrothermal pools: a scenario to guide experimental approaches to the origin of cellular life. Life 5:872–887

  15. Dibrova D, Makarova K, Galperin M, Koonin E, Mulkidjanian A (2011) Comparative analysis of lipid biosynthesis in Archaea and Bacteria: what was the structure of first membrane lipids. In: Proceedings of the international Moscow conference on computational molecular biology July 21–24

  16. Du Y, Cai F, Kong D-L, He L-N (2005) Organic solvent-free process for the synthesis of propylene carbonate from supercritical carbon dioxide and propylene oxide catalyzed by insoluble ion exchange resins. Green Chem. Accessed 20 June 2019

  17. Fani R, Fondi M (2009) Origin and evolution of metabolic pathways. Phys Life Rev 6:23–52

  18. Ferrer-Tasies L, Moreno-Calvo E, Cano-Sarabia M, Aguilella-Arzo M, Angelova A, Lesieur S, Ricart S, Faraudo J, Ventosa N, Veciana J (2013) Quatsomes: vesicles formed by self-assembly of sterols and quanternary ammonium surfactants. Langmuir 29:6519–6528.

  19. Furukawa Y, Honjo M (1968) A novel method for the synthesis of purine nucleosides using Friedel-Crafts catalysts. Chem Pharm Bull 16:1076–1080

  20. Gagliardi CJ, Vannucci AK, Concepcion JJ, Chen Z, Meyer TJ (2012) The role of proton coupled electron transfer in water oxidation. Energy Environ Sci 5:7704–7717

  21. Gilbert W (1986) Origin of life: the RNA world. Nature 319:618

  22. Glansdorff N, Xu Y, Labeddan B (2008) The last universal common ancestor: emergence, constitution and genetic legacy of an elusive forerunner. Biol Direct 3:29–64

  23. Hargreaves WR, Deamer DW (1978) Liposomes from ionic, single-chain amphiphiles. Biochem 17(18):3759–3768

  24. Kim SC, O’Flaherty DK, Zhou L, Lelyveld VS, Szostak JW (2018) Inosine, but none of the 8-oxo-purines, is a plausible component of a primordial version of RNA. PNAS 115(52):13318–13323

  25. Krishnamurthy R (2015) On the emergence of RNA. Isr J Chem 55:837–850

  26. Lancet D, Zidovetzki SR, Markovitch O (2018) Systems protobiology: origin of life in lipid catalytic networks. J R Soc Interface 15.

  27. Laxer A, Major DT, Gottlieb HE, Fischer B (2001) (15N5)-labeled adenine derivatives: synthesis and studies of tautomerism by 15N NMR spectroscopy and theoretical calculations. J Org Chem 66:5463–5481

  28. Lu X-B, He R, Bai C-X (2002) Synthesis of ethylene carbonate from supercritical carbon dioxide/ethylene oxide mixture in the presence of bifunctional catalyst. J Mol Catal A Chem 186:1–11

  29. Lubczak R, Duliban J (2002) A study of the reaction of adenine with ethylene oxide or either ethylene carbonate. React Funct Polym 52:127–134

  30. Luisi PL, Rasi PSS, Fabio M (2004) A possible route to prebiotic vesicle reproduction. Artif Life 10:297–308

  31. Marek R, Brus J, Tousek J, Kovacs L, Hocková D (2002) N7- and N9-substituted purine derivatives: a 15N NMR study. Magn Reson Chem 40:353–360.

  32. Mayer C, Schreiber U, Dávila MJ (2017) Selection of prebiotic molecules in amphiphilic environments. Life 2017(7):3. Accessed 31 May 2019

  33. Meyers VC (1910) On the salts of cytosine, thymine and uracil. J Biol Chem 7:249–258

  34. Mikulski CM, Cocco S, De Franco N, Moore T, Nicholas M, Karayannis MK (1985) Adenine complexes with divalent 3d metal chlorides. Inorg Chim Acta 106(2):89–95.

  35. Morel AC, Choquesillo-Lazarte D, Alarcoon-Payer C, Gonzaalez-Peerez JM, Castinneiras A, Nicloos-Gutieerrez J (2002) An aqua-adenine H-bonding interaction controlling the formation of the rare Zn (II)–N9(adenine) bond in crystal structure of diaqua(adenine)(iminodiacetato)zinc (II). Inorg Chem Commun 6:1354–1357

  36. Muchowska KB, Varma SJ, Moran J (2019) Synthesis and breakdown of universal metabolic precursors promoted by iron. Nature 569:104–107

  37. Mulkidjanian AY, Galperin MY (2010) Evolutionary origins of membrane proteins. In: Structural bioinformatics of membrane proteins. Springer, Vienna

  38. Mulkidjanian AY, Galperin MY, Koonin V (2009) Co-evolution of primordial membranes and membrane proteins. Trends Biochem Sci 3(4):206–215

  39. Nakano K, Sumitomo Y, Kondo K (1997) Tautomerism polymerization: new degradable polyethers and polythioehters from nucleic acid base derivatives. Macromolecules 30:852–856

  40. North M, Villuendas P, Young C (2009) A gas-phase flow reactor for ethylene carbonate synthesis from waste carbon dioxide. Chem Eur J 15:11454–11457

  41. Patel A (2005) The triplet genetic code had a doublet predecessor. J Theor Biol 233:527–532

  42. Pohorille A, Deamer D (2009) Self-assembly and function of primitive cell membranes. Res Microbiol 160:449–456

  43. Prystaš M, Gut J (1962) Nucleic acid components and their analogues. XVII. Reaction of uracil and of its aza analogues with ethylene carbonate. CCCC 27:1054–1056

  44. Raine DJ, Norris V (2007) Lipid domain boundaries as prebiotic catalysts of peptide bond formation. J Theor Biol 246:176–185

  45. Rutledge LR, Churchill DM, Wetmore SD (2010) A preliminary investigation of the additivity of π-- π or π+--π stacking and T-shaped interactions between natural or damaged DNA nucleobases and histidine. J Phys Chem 114:3355–3367

  46. Schein AH (1962) 6-Acylamido- and 6-Acylamido-9(or 7)-acylpurines. J Med Chem 5:302–311.

  47. Schreiber U, Locker-Grütjen O, Mayer C (2012) Hypothesis: origin of life in deep-reaching tectonic faults. Orig Life Evol Biosph 42:47–54.

  48. Segre D, Ben-Eli D, Deamer DW, Lancet D (2001) The lipid world. Orig Life Evol Biosph 31:119–145

  49. Shonle HA, Row PQ (1921) New benzyl esters possessing an anti-spasmodic action. J Am Chem Soc 43(2):361–365

  50. Simoneit BRT (2003) Prebiotic organic synthesis under hydrothermal conditions: an overview. Adv Space Res 33:88–94

  51. Speca AN, Mikulski CM, Iaconianni FJ, Pytlewski LI, Karayannis NM (1981) Characterization studies of adenine complexes with 3d metal perchlorates. J Inorg Nucl Chem 43(11):2771–2779.

  52. Sproul GD (2015) Abiogenic syntheses of lipoamino acids and lipopeptides and their prebiotic significance. Orig Life Evol Biosph 45:427–437.

  53. Sturgis JN (2011) Peptide-dominated vesicles: bacterial internal membrane compartments as model systems for prebiotic evolution. In: Egel R et al (eds) Origins of life: the primal self-organization. Springer, Berlin/Heidelberg.

  54. Ustyuzhanin GE, Kolomeitseva GE, Tikhomirova-Sidorova NS (1978) Hydroxyethylation of uracil, adenine, and cytosine with ethylene carbonate. Chem Heterocycl Compd 14(5):562–566

  55. Van der Gulik PTS, Speijer D (2018) How amino acids and peptides shaped the RNA world. Life 5:230–246

  56. Van Mooy BAS, Fredricks HF, Pedler BE, Dyhrman ST, Karl DM, Koblizek M, Lomas MW, Mincer TJ, Moore LR, Moutin T, Rappe MS, Webb EA (2009) Phytoplankton in the ocean use non-phosphorus lipids in response to phosphorus scarcity. Nature 458:69–72

  57. Vărăşteanu D, Piscureanu A, Chcan IE, Corobea MC (2011) Aspects regarding the synthesis and surface properties of some glycine based surfactants. UPB Sci Bull Ser B 73:147–154

  58. Wachtershauser G (1990) Evolution of the first metabolic cycles. Proc Natl Acad Sci U S A 87:200–204

  59. Walde P (2006) Surface assemblies and their various possible roles for the origin(s) of life. Orig Life Evol Biosph 36:109–150

  60. Wamberg MC, Pedersen PL, Loffler PMG, Albertsen AN, Maurer SE, Nielsen KA, Monnard P-A (2017) Synthesis of lipophilic guanine N-9 derivatives: membrane anchoring of nucleobases tailored to fatty acid vesicles. Bioconjug Chem 28:1893–1905

  61. Watson JD, Crick FHC (1953) Molecular structure of nucleic acids: a structure for deoxyribose nucleic acid. Nature 171:737–738

  62. Wieczorek R, Adamala K, Gasperi T, Polticelli F (2017) Small random peptides: an unexplored reservoir of potentially functional primitive organocatlysts: the case of seryl-histidine. Life 7(2):pii: E19.

  63. Zaia DAM (2004) A review of adsorption of amino acids on minerals: was it important for origin of life? Amino Acids 27:113–118

Download references


Dr. Tim Roy, Research Associate at USCB, provided GC/MS data collection and analysis as well as valuable discussions and insights; Prof. Charles Keith, Distinguished Professor Emeritus from USCB, photographed microscopic images of lipids and amphiphiles; Suzanne Wolf prepared microphotographs; Associate Professor Edward D’Antonio produced chemical reaction diagrams, and numerous USCB Information Technology specialists provided technical assistance. We gratefully acknowledge the use of USCB laboratories and equipment for this study.

Author information

Correspondence to Gordon D. Sproul.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Electronic Supplementary Material


(XLSX 78 kb)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Sproul, G.D. Membranes Composed of Lipopeptides and Liponucleobases Inspired Protolife Evolution. Orig Life Evol Biosph 49, 241–254 (2019).

Download citation


  • Amphiphile
  • Codon
  • Evolution
  • Lipopeptide
  • Prebiotic
  • Vesicle