PREBIOTIC CHEMISTRY

1. PREBIOTIC CHEMISTRY

2. Biophysic course WS 2006, Rome. 1.Science confronting the origin of life on Earth. 1.2.: Prebiotic chemistry

3. 1. Life originated from inanimate matter as a spontan- eous and continous increase of molecular complexity. Chemical continuity principle - no transcendental principle. 2. The chemical process(es) to transition to life can be reproduced in the laboratory with the presently available chemical techniques and chemicals. 3. And this can be implemented in a reasonable (hours or max. days) experimental time span - once you know the right combination of prebiotic compounds and theconditions. 4. Since there is no documentation on how things really happened, there is no obligatory research pathway. SOME MAIN ASSUMPTIONS OF PRESENT DAY RESEARCH ON THE ORIGIN OF LIFE LIFE inanimate matter

4. Lightnings_SV3.avi

6. Chemistry of HCN, precursor of purines Ferris & Orgel 1996, 1967

7. Synthesis of purines Oró, 1960

8. Synthesis of sugar phosphates Eschenmoser 1988, 1990

9. Activation of aminoacids by the N-carboxyanhydride and their condensation.

10. Why do aminoacid form in Miller‘ experiment? Why this...and not that?.... They form because there are the most stable of the possible compounds- due to processes under thermodynamic control

11. OTHER SOURCES OF ORGANICS a considerable enrichment of prebiotic moieties may have come from submarine vents and other hydrothermal sources (see for example Miller and Bada, 1988; Holm and Andersson, in Brack, 1998; Stetter, in Brack, 1998). One should start from the 1979 discovery of deep-sea vents with black smokers which are associated with an extraordinary abundance of the most phylogenetically primitive organisms on Earth.

12. OTHER SURCES OF ORGANICS The present amount of space dust falling on Earth amounts to ca. 40,000 tons per year, which sounds impressive. This, spread over all Earth surface, corresponds to only 8 × 10-9 g/cm2 per year (Love and Brownlee, 1993), and the percentage of organics may be tiny (Miller, 1998; Oro et al., 2002). On the other hand, accumulation over billions of years can bring to a considerable amount of matter.

13. OTHER SOURCES OF ORGANICS aminoacids are present in meteorites (Epstein et al., 1987; Pizzarello et al., 1994; Pizzarello and Cronin, 2000; Pizzarello and Weber, 2004). In this regard, of particular interest is the report about -methyl aminoacids, which have been found in the L enantiomeric excess in Murchnson and Murray meteorites (Cronin and Pizzarello, 1997). These compounds are particularly resistant to racemization,

14. Major Sources (in kg/yr) of Prebiotic Organic Compounds in the Early Earth (from Oro et al., 2002) Terrestrial Sources kg/yr* UV Photolysis1 Electric Discharge2 Shocks from impacts3 Hydrothermal Vents4 3 × 108 3 × 107 4 × 102 1 × 108 Extraterrestrial Sources5 IDP’s Comets 2 × 108 1 × 1011 Total 1011

15. ·Assumes intermediate atmosphere, defined as [H2]/[CO2] = 0.1. ·IDP= interplanetary dust. 1 Synthesis of the Miller-Urey type. 2 Such as that caused by lightning interacting with a volcanic discharge. 3 An estimate for compounds created from the interaction between infalling objects and the Earth’s atmosphere. 4 Based on present-day estimates for total organic matter in hydrothermal vent effluent. 5 Conservative estimate based on possible cumulative input calculated assuming flux of 1022 kg of cometary material during first Ga (109 years) of Earth’s history. If comets contain on the order of 15 wt% organic material, and if ≈ 10% of this material survives, it will comprise approximately 1011 kg yr-1 average flux via comets during the first 109 years.

16. PREBIOTIC CHEMISTRY HAS REACHED CONSIDERABLE SUCCESS ..... BUT Even if the chemist would have access to all prebiotic bio-monomers he would NOT have the solution to the origin of life

17. THE CORE OF THE PROBLEM: LIFE AS WE KNOW IT IS DETERMINED BY SPECIFIC MACROMOLECULAR SEQUENCES LIKE NUCLEIC ACIDS AND PROTEINS

18. C O N H C H C O N H C H C O N H C H R R R 1 2 3 X Y Z P Y O P O R i b O P O R i b O P O R i b O B a s e B a s e B a s e 1 2 3

21. A-DNA B-DNA Z-DNA

23. The macromolecules of life are not there because they are more stable than their billions of constitutional isomers They–and/or their precursors- are the products of statistics and contingency in the polymerization processes and evolution

26. Cast the dice again and........ And you will get a different set of macromolecules that do not necessarily support life

27. QUESTIONS: HOW AND WHY „OUR“ PROTEINS HAVE BEEN SELECTED? ARE THE PROTEINS OF LIFE THE ONLY ONES THAT COULD BE FORMED- AND GAVE ORIGIN TO LIFE BY A DETERMINISTIC (OBLIGATORY) SERIES OF EVENTS OR ARE THEY THE PRODUCT OF CONTINGENCY(CHANCE) AND LIFE IS ALSO A PRODUCT OF CONTINGENCY?

28. PROJECT RANDOM POLYPEPTIDES: MAKE A VASTE LIBRARY OF RANDOM DE NOVO PROTEINS ASK THE QUESTION: HOW MANY OF THEM WILL BE FOLDED? Folding is the prerequisiste for any intelligent function by proteins

29. Helper Phage Modified Phage gene 3 fusion protein Plasmidic DNA ss DNA gene 3 fusion PHAGEMID VECTOR SYSTEM IN PHAGE DISPLAY

30. STRATEGY FOR THE ISOLATION OF FOLDED PEPTIDES mAB TAG Thrombin Cleavage Site Random Peptide (50mer) pIII Phage

31. ANALYSIS OF THE PEPTIDE PHAGE LIBRARY Library 1.98 x 109 clones 180 clones were randomly selected 44% correct insert (79 clones) 73 clones tested for thrombin stability

32. DISTRIBUTION OF THE PEPTIDE LIBRARY WITH RESPECT TO THROMBIN DIGESTION “Stable” “Unstable” % of the73 clones of the phage library % digestion categories