The chemistry of life’origins: II. From the building blocks to life

1. The chemistry of life’origins: II. From the building blocks to life

2. CHONS + H2O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes Clays? 

3. Polymer formation in water Formally, the formation of a biopolymer consists to eliminate water molecules between monomer units. However, the formation of either polyamino acids or polynucleotides from their monomers is not energetically favored. In water, energy is required to link 2 amino acids. For example, the free energy for the condensation of alanine and glycine to form the dipeptide alanyl-glycine in water is 4.13 Kcal/mol at 37°C and pH 7: H-Ala-OH + H-Gly-OH  H-Ala-Gly-OH + H2O G0 =4.13 Kcal The thermodynamic barrier is very large for the formation of a long chain polyamino acid. For example, 1 M solutions in each of the 20 protein amino acids would yield at equilibrium a 10-99 M concentration for a 12 000 Dalton protein. To yield one protein at equilibrium, the volume of the solution would have to be 1050 times the volume of the Earth! So energy input was necessary to make polynucleotides and polyamino acids in the primitive oceans.

4. Alanine NCA

6. Glu-SET & bicarbonate Glu-SEt Glu-oligomers obtained in the presence of bicarbonate via the intermediate formation of a carbamate –OOC-NH-CHR-CO-SET and probably a Leuch’s anhydride.

9. Polymerization of H-Leu-SEt in the presence of different mineral surfaces (15 days, pH 8, 25 C) n H–Leu–S–C2H5 H–Leun–S–C2H5 + nHS–C2H5 H–Leun–S–C2H5 + H2O  H–Leun–OH + HS–C2H5 1-SEt DKP 2-OH 2-SEt 3-OH 3-SEt 4-OH 4-SEt Blank 8.7 68.1 7.6 0.6 0 8.8 0 6.2 Clay 38.2 0 40.1 6.5 0 0 2.6 0 CdS 12.4 54.5 1.4 3.4 1.9 19.4 0 7 FeS 90.5 1.8 0 5.8 0 0 0 0 ZnS 24.2 30.6 0 4.2 0 14.3 0 13.8 Polymerization of H-Leu-SEt in the presence of different mineral surfaces (15 days, pH 8, 25 C)

10. 1-SEt DKP 2-OH 2-SEt 3-OH 4-OH 5-OH 6-OH 7-OH 25 C 12.4 54.5 1.4 3.4 1.9 0 0 0 0 Wet/dry 2.6 3.5 28.7 7 1.7 0 11.3 31.3 13.9 Polymerization of H-Leu-SEt in the presence of CdS using wet/dry cycles (12 hr at 25 C / 12 hr at 80 C for 2 weeks, pH 8).

11. Rainbow submarine hydrothermal system

12. Polymerization of amino thioesters on hydrothermal sediments n H–Leu–S–C2H5 H–Leun–S–C2H5 + nHS–C2H5 H–Leun–S–C2H5 + H2O  H–Leun–OH + HS–C2H5 control 2 >4 1 4 DKP 3

13. Flow reactor simulating a submarine hydrothermal system

14. The β-sheet structure of alternating hydrophilic / hydrophobic peptides

15. Formation of double layer β-sheets of alternating hydrophobic/hydrophilic polypeptides, driven by hydrophobic clustering of side-chains.

17. β-sheets are more stable than α-helices

18. The hydrophobic amino acid must be strongly hydrophobic

19. 20 °C 60 °C Higher temperatures favor β-sheet structures α 58% 34% Poly(Leu50, Lys50) which exhibits random coil, α- and β-geometries, develops more β-structures with increasing temperature. β 27% 51% random 16% 15%

21. The β-sheet structure of alternating hydrophilic / hydrophobic peptides

22. Percentage of β-sheets with increasing L-enantiomers

24. 77%L  84%L 86%L  92%L 95%L  99%L

25. The alternating polypeptide poly(Glu-Leu) is randomly coiled in water. • It adopts: • a β-sheet structure in the presence of traces of CaCl2 • but • - an α–helix in the presence of FeCl3.

28. Even more interestingly, poly(Glu-Leu) is also capable of extracting • cations from insoluble minerals and adopts an ordered conformation: • a β-sheet structure in the presence of CdS • an α–helix in the presence of molybdenum • Peptides with 10-amino acids are long enough to significantly adsorb • onto the mineral surface. • Montmorillonite adsorbs the peptide but does not induce any • conformational change.

29. Poly(Leu-Lys) catalyses the cleavage of RNA phosphodiester bonds, providing a rate enhancement of 185, compared to the control. The decapeptide is long enough to exhibit the catalytic activity. Poly(Pro-Leu-Lys-Leu-Lys) and poly(D,L Leu - D,L Lys) are inactive (rate enhancement of 11 and 17, resp.). Control + poly(Leu-Lys)

30. CONCLUSION Stable short β-sheet forming peptides were probably abundant in the primitive oceans Doing what?

31. CHONS + H2O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes

32. Heterocyclic base (adenine) Sugar (ribose) Phosphate A nucleotide, the basic constituent of RNA

33. RNA ribose (peak 8) is poorly formed from formaldehyde

34. Chemical self-replication works beautifully with preformed RNA strands

35. Are clays of any help?

36. With CDI

37. RNA Pyranosyl-RNA, p-RNA • P-RNA: • base pairs more strongly than RNA • the twist of the helices is less important • self-organisation and stereoselective polymerisation • of p-ATCG tetramers

38. RNA Threose-RNA, TNA • TNA: • is more stable to hydrolysis than RNA • forms TNA-TNA double helices • forms TNA-RNAhybrid duplexes with RNA

39. Peptide nucleic acid, PNA • PNA: • has a 2-aminoethyl glycine backbone • forms PNA-PNA double helices • forms PNA-RNA hybrid double helices

40. CHONS + H2O  Robots or catalysts  RNA world Viruses?  Cells, i.e. RNA proteins membranes

41. Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements

44. Autocatalytic growth of micelles: primitive life?

45. A self-replicating peptide? Reza Ghadiri showed that the 32-residue α-helical peptide autocatalytically templates its own synthesis by accelerating the amide bond condensation of 15- and 17-residue fragments. The 32-residue peptide replicator is capable of efficiently amplifying homochiral products from a racemic mixture of peptides fragments

46. Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements

47. Cross-inhibition in template-directed polymerisation of activated L,D nucleotides

48. Autocatalytic growth of Glu-oligomers on short α-helices with an active ester of Glu in benzene

49. Autocatalytic growth of Glu-oligomers on short α-helices

50. Catalysis Autocatalysis Self-replication: autocatalysis + selection of bifunctional elements