Carbonyl Sulfide as a Prebiotic Activation Agent for Stereo- and Sequence-Selective, Amyloid-Templated Peptide Elongation


Prebiotic chemical replication is a commonly assumed precursor to and prerequisite for life and as such is the one of the goals of our research. We have previously reported on the role that short peptide amyloids could have played in a template-based chemical elongation. Here we take a step closer to the goal by reproducing amyloid-templated peptide elongation with carbonyl sulfide (COS) in place of the less-prebiotically relevant carbonyldiimidazole (CDI) used in the earlier study. Our investigation shows that the sequence-selectivity and stereoselectivity of the amyloid-templated reaction is similar for both activation chemistries. Notably, the amyloid protects the peptides from some of the side-reactions that take place with the COS-activation.

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  1. Bhushan R, Brückner H (2004) Marfey’s reagent for chiral amino acid analysis: a review. Amino Acids 27:231–247.

  2. Blair NE, Bonner WA (1980) Experiments of the amplification of optical activity. Orig Life Evol Biosph 10:255–263.

  3. Bomba R, Kwiatkowski W, Sánchez-Ferrer A, Riek R, Greenwald J (2018) Cooperative induction of ordered peptide and fatty acid aggregates. Biophys J 115:2336–2347.

  4. Carny O, Gazit E (2005) A model for the role of short self-assembled peptides in the very early stages of the origin of life. FASEB J 19:1051–1055.

  5. Childers WS, Mehta AK, Lu K, Lynn DG (2009) Templating molecular arrays in Amyloid’s cross-β grooves. J Am Chem Soc 131:10165–10172.

  6. Chiti F, Dobson CM (2006) Protein Misfolding, functional amyloid, and human disease. Annu Rev Biochem 75:333–366.

  7. Dale T (2006) Protein and nucleic acid together: a mechanism for the emergence of biological selection. J Theor Biol 240:337–342.

  8. Ehler KW, Orgel LE (1976) N,N′-carbonyldiimidazole-induced peptide formation in aqueous solution. Biochimica et Biophysica Acta (BBA) - Protein Structure 434:233–243.

  9. Ehler KW, Girard E, Orgel LE (1977) Reactions of polyfunctinal amino acids with N,N’-carbonyldiimidazole in aqueous solution-oligopeptide formation. Biochim Biophys Acta 491:253–264. Reactions of polyfunctional amino acids with N,N'-carbonyldiimidazole in aqueous solution--oligopeptide formation

  10. Friedmann MP, Torbeev V, Zelenay V, Sobol A, Greenwald J, Riek R (2015) Towards prebiotic catalytic amyloids using high throughput screening. PLoS One 10:e0143948.

  11. Greenwald J, Riek R (2010) Biology of amyloid: structure, function, and regulation. Structure 18:1244–1260.

  12. Greenwald J, Riek R (2012) On the possible amyloid origin of protein folds. J Mol Biol 421:417–426.

  13. Hein JE, Gherase D, Blackmond DG (2013) Chemical and physical models for the emergence of biological Homochirality. In: Cintas P (ed) Biochirality: origins. Evolution and Molecular Recognition. Springer, Berlin Heidelberg, Berlin, Heidelberg, pp 83–108

  14. Hitz TH, Luisi PL (2004) Spontaneous onset of Homochirality in Oligopeptide chains generated in the polymerization of N-Carboxyanhydride amino acids in water. Orig Life Evol Biosph 34:93–110.

  15. Kuipers BJH, Gruppen H (2007) Prediction of molar extinction coefficients of proteins and peptides using UV absorption of the constituent amino acids at 214 nm to enable quantitative reverse phase high-performance liquid chromatography-mass spectrometry analysis. J Agric Food Chem 55:5445–5451.

  16. Lara C, Handschin S, Mezzenga R (2013) Towards lysozyme nanotube and 3D hybrid self-assembly. Nanoscale 5:7197–7201.

  17. Leman L, Orgel L, Ghadiri MR (2004) Carbonyl sulfide-mediated prebiotic formation of peptides. Science 306:283–286.

  18. Makhlynets OV, Gosavi PM, Korendovych IV (2016) Short self-assembling peptides are able to bind to copper and activate oxygen. Angew Chem Int Ed 55:9017–9020.

  19. Maury CPJ (2009) Self-propagating β-sheet polypeptide structures as prebiotic informational molecular entities: the amyloid world. Orig Life Evol Biosph 39:141–150.

  20. Meersman F, Dobson CM (2006) Probing the pressure-temperature stability of amyloid fibrils provides new insights into their molecular properties. Biochimica et Biophysica Acta (BBA) – Proteins and Proteomics 1764:452–460.

  21. Mehta AK, Lu K, Childers WS, Liang Y, Dublin SN, Dong J, Snyder JP, Pingali SV, Thiyagarajan P, Lynn DG (2008) Facial symmetry in protein self-assembly. J Am Chem Soc 130:9829–9835.

  22. Omosun TO, Hsieh M-C, Childers WS et al (2017) Catalytic diversity in self-propagating peptide assemblies. Nat Chem 9:805–809.

  23. Reches M, Gazit E (2003) Casting metal nanowires within discrete self-assembled peptide nanotubes. Science 300:625–627.

  24. Rout SK, Friedmann MP, Riek R, Greenwald J (2018) A prebiotic template-directed peptide synthesis based on amyloids. Nat Commun 9:234.

  25. Rubinstein I, Eliash R, Bolbach G, Weissbuch I, Lahav M (2007) Racemic β sheets in Biochirogenesis. Angew Chem Int Ed 46:3710–3713.

  26. Rufo CM, Moroz YS, Moroz OV, Stöhr J, Smith TA, Hu X, DeGrado W, Korendovych IV (2014) Short peptides self-assemble to produce catalytic amyloids. Nat Chem 6:303–309.

  27. Sánchez-Ferrer A, Adamcik J, Handschin S et al (2018) Controlling Supramolecular chiral nanostructures by self-assembly of a biomimetic β-sheet-rich Amyloidogenic peptide. ACS Nano.

  28. Tsuruta T, Inoue S, Matsuura K (1967) Asymmetric selection in the copolymerization of N-carboxy-L- and D-alanine anhydride. Biopolymers 5:313–319.

  29. Zhang C, Xue X, Luo Q, Li Y, Yang K, Zhuang X, Jiang Y, Zhang J, Liu J, Zou G, Liang XJ (2014) Self-assembled peptide Nanofibers designed as biological enzymes for catalyzing Ester hydrolysis. ACS Nano 8:11715–11723.

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Correspondence to Roland Riek or Jason Greenwald.

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Bomba, R., Rout, S.K., Bütikofer, M. et al. Carbonyl Sulfide as a Prebiotic Activation Agent for Stereo- and Sequence-Selective, Amyloid-Templated Peptide Elongation. Orig Life Evol Biosph 49, 213–224 (2019) doi:10.1007/s11084-019-09586-5

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  • Origin of life
  • Carbonyl sulfide
  • Amyloid
  • Templated peptide synthesis