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Orgel, L. E.

Publications and source records attributed to Orgel, L. E..

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS1998

Polymerization on the rocks: theoretical introduction

It is difficult if not impossible to synthesize long polymers of amino acids, nucleotides, etc., in homogeneous aqueous solution. We suggest that long polymers were synthesized on the surface of minerals in a prebiotic process analogous to solid-phase synthesis. Provided that the affinity of a mineral for an oligomer increases with the length of the oligomer, adsorption must become essentially irreversible for sufficiently long oligomers. Irreversibly adsorbed oligomers may be elongated indefinitely by repeated cycles in which the mineral with its adsorbed oligomers is first incubated with activated monomers and then washed free of deactivated monomer and side-products. We discuss in some detail the formation of oligomers of negatively-charged amino acids such as glutamic acid on anion-exchange minerals such as hydroxylapatite or illite. We show that the average length of adsorbed oligomers at steady state, n, depends on the balance between the rate of chain elongation and the rate of hydrolysis, and we derive a very approximate formula for n.

NASA Discipline Exobiology↗
NASA NTRS1998

The origin of life--how long did it take?

We do not understand the steps leading from the abiotic early earth to the RNA world. Consequently, we cannot estimate the time required for the origins of life. Attempts to circumvent this essential difficulty are based on misunderstandings of the nature of the problem.

NASA Discipline Exobiology↗
NASA NTRS1998

Polymerization of beta-amino acids in aqueous solution

We have compared carbonyl diimidazole (CDI) and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as activating agents for the oligomerization of negatively-charged alpha- and beta-amino acids in homogeneous aqueous solution. alpha-Amino acids can be oligomerized efficiently using CDI, but not by EDAC. beta-Amino acids can be oligomerized efficiently using EDAC, but not by CDI. Aspartic acid, an alpha- and beta-dicarboxylic acid is oligomerized efficiently by both reagents. These results are explained in terms of the mechanisms of the reactions, and their relevance to prebiotic chemistry is discussed.

NASA Discipline Exobiology↗
NASA NTRS1998

Formation of oligonucleotide-PNA-chimeras by template-directed ligation

DNA sequences have previously been reported to act as templates for the synthesis of PNA, and vice versa. A continuous evolutionary transition from an informational replicating system based on one polymer to a system based on the other would be facilitated if it were possible to form chimeras, that is molecules that contain monomers of both types. Here we show that ligation to form chimeras proceeds efficiently both on PNA and on DNA templates. The efficiency of ligation is primarily determined by the number of backbone bonds at the ligation site and the relative orientation of template and substrate strands. The most efficient reactions result in the formation of chimeras with ligation junctions resembling the structures of the backbones of PNA and DNA and with antiparallel alignment of both components of the chimera with the template, that is, ligations involving formation of 3'-phosphoramidate and 5'-ester bonds. However, double helices involving PNA are stable both with antiparallel and parallel orientation of the two strands. Ligation on PNA but not on DNA templates is, therefore, sometimes possible on templates with reversed orientation. The relevance of these findings to discussions of possible transitions between genetic systems is discussed.

NASA Discipline Exobiology↗
NASA NTRS1997

Prebiotic phosphorus chemistry reconsidered

The available evidence indicates that the origin of life on Earth certainly occurred earlier than 3.5 billion years ago and perhaps substantially earlier. The time available for the chemical evolution which must have preceded this event is more difficult to estimate. Both endogenic and exogenic contributions to chemical evolution have been considered; i.e., from chemical reactions in a primitive atmosphere, or by introduction in the interiors of comets and/or meteorites. It is argued, however, that the phosphorus chemistry of Earth's earliest hydrosphere, whether primarily exogenic or endogenic in origin, was most likely dominated by compounds less oxidized than phosphoric acid and its esters. A scenario is presented for the early production of a suite of reactive phosphonic acid derivatives, the properties of which may have foreshadowed the later appearance of biophosphates.

NASA Discipline Exobiology↗
NASA NTRS1997

Information transfer from peptide nucleic acids to RNA by template-directed syntheses

Peptide nucleic acids (PNAs) are uncharged analogs of DNA and RNA in which the ribose-phosphate backbone is substituted by a backbone held together by amide bonds. PNAs are interesting as models of alternative genetic systems because they form potentially informational base paired helical structures. A PNA C10 oligomer has been shown to act as template for efficient formation of oligoguanylates from activated guanosine ribonucleotides. In a previous paper we used heterosequences of DNA as templates in sequence-dependent polymerization of PNA dimers. In this paper we show that information can be transferred from PNA to RNA. We describe the reactions of activated mononucleotides on heterosequences of PNA. Adenylic, cytidylic and guanylic acids were incorporated into the products opposite their complement on PNA, although less efficiently than on DNA templates.

NASA Discipline Exobiology↗
NASA NTRS1997

Information transfer from DNA to peptide nucleic acids by template-directed syntheses

Peptide nucleic acids (PNAs) are analogs of nucleic acids in which the ribose-phosphate backbone is replaced by a backbone held together by amide bonds. PNAs are interesting as models of alternative genetic systems because they form potentially informational base paired helical structures. Oligocytidylates have been shown to act as templates for formation of longer oligomers of G from PNA G2 dimers. In this paper we show that information can be transferred from DNA to PNA. DNA C4T2C4 is an efficient template for synthesis of PNA G4A2G4 using G2 and A2 units as substrates. The corresponding synthesis of PNA G4C2G4 on DNA C4G2C4 is less efficient. Incorporation of PNA T2 into PNA products on DNA C4A2C4 is the least efficient of the three reactions. These results, obtained using PNA dimers as substrates, parallel those obtained using monomeric activated nucleotides.

NASA Discipline Exobiology↗
NASA NTRS1997

Oxidative acylation using thioacids

Several important prebiotic reactions, including the coupling of amino acids into polypeptides by the formation of amide linkages, involve acylation. Theae reactions present a challenge to the understanding of prebiotic synthesis. Condensation reactions relying on dehydrating agents are either inefficient in aqueous solution or require strongly acidic conditions and high temperatures. Activated amino acids such as thioester derivatives have therefore been suggested as likely substrates for prebiotic peptide synthesis. Here we propose a closely related route to amide bond formation involving oxidative acylation by thioacids. We find that phenylalanine, leucine and phenylphosphate are acylated efficiently in aqueous solution by thioacetic acid and an oxidizing agent. From a prebiotic point of view, oxidative acylation has the advantage of proceeding efficiently in solution and under mild conditions. We anticipate that oxidative acylation should prove to be a general method for activating carboxylic acids, including amino acids.

Non-NASA Center↗
NASA NTRS1997

Efficient oligomerization of negatively-charged beta-amino acids at -20 degrees C

This paper describes a procedure, known as eutectic concentration, used to concentrate an aqueous solution by cooling. Using a water-soluble carbodiimide, 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide, the researchers were able to accelerate the rate of polymerization of beta-amino acids when the solution was cooled to -20 degrees C. Different temperatures and solution concentrations were investigated to determine which gave the most efficient rates of polymerization. The effect of sodium chloride on the products of the reaction was also studied.

Non-NASA Center↗
NASA NTRS1995

Template switching between PNA and RNA oligonucleotides

The origin of the RNA world is not easily understood, as effective prebiotic syntheses of the components of RNA, the beta-ribofuranoside-5'-phosphates, are hard to envisage. Recognition of this difficulty has led to the proposal that other genetic systems, the components of which are more easily formed, may have preceded RNA. This raises the question of how transitions between one genetic system and another could occur. Peptide nucleic acid (PNA) resembles RNA in its ability to form double-helical complexes stabilized by Watson-Crick hydrogen bonding between adenine and thymine and between cytosine and guanine, but has a backbone that is held together by amide rather than by phosphodiester bonds. Oligonucleotides bases on RNA are known to act as templates that catalyse the non-enzymatic synthesis of their complements from activated mononucleotides, we now show that RNA oligonucleotides facilitate the synthesis of complementary PNA strands and vice versa. This suggests that a transition between different genetic systems can occur without loss of information.

NASA Discipline Exobiology↗
NASA NTRS1995

Oligonucleotides as probes for studying polymerization reactions in dilute aqueous solution: II. Polycondensations

We have prepared a [32P]-labeled oligonucleotide probe carrying a ureido (-NH-CO-NH2) function at its 3'-terminus. This labeled oligomer was used to study polycondensations of urea and formaldehyde and of various phenols and formaldehyde in aqueous solution. The formation of formaldehyde copolymers attached to the amido-function of the probe was monitored by gel electrophoresis. Our results are generally in agreement with those obtained using conventional techniques. Our method is suitable for monitoring potentially prebiotic polycondensation reactions involving formaldehyde.

NASA Discipline Exobiology↗
NASA NTRS1994

Oligonucleotides as probes for studying polymerization reactions in dilute aqueous solution

We have prepared a [32P]-labled oligonucleotide probe carrying a free primary amine at its 3'-terminus. This probe is used to initiate polymerization of aziridine (ethyleneimine) in aqueous solution. The nature of the oligomeric products and the kinetics of their formation are then monitored by gel electrophoresis. Our results are generally consistent with those obtained using conventional techniques. We have also investigated the effect of polyanionic templates on the rate of oligomerization of aziridine. We find that water-soluble polyanions generally accelerate the polymerization. The sodium salt of polymethacrylic acid is the most effective of the templates that we studied. The methods introduced in this paper should be applicable to a variety of polymerization reactions in aqueous solution. They should greatly simplify the screening of potentially prebiotic polymerization reactions.

NASA Discipline Exobiology↗
NASA NTRS1992

Nonenzymatic template-directed synthesis on hairpin oligonucleotides. 3. Incorporation of adenosine and uridine residues

We have used [32P]-labeled hairpin oligonucleotides to study template-directed synthesis on templates containing one or more A or T residues within a run of C residues. When nucleoside-5'-phosphoro(2-methyl)imidazolides are used as substrates, isolated A and T residues function efficiently in facilitating the incorporation of U and A, respectively. The reactions are regiospecific, producing mainly 3'-5'-phosphodiester bonds. Pairs of consecutive non-C residues are copied much less efficiently. Limited synthesis of CA and AC sequences on templates containing TG and GT sequences was observed along with some synthesis of the AA sequences on templates containing TT sequences. The other dimer sequences investigated, AA, AG, GA, TA, and AT, could not be copied. If A is absent from the reaction mixture, misincorporation of G residues is a significant reaction on templates containing an isolated T residue or two consecutive T residues. However, if both A and G are present, A is incorporated to a much greater extent than G. We believe that wobble-pairing between T and G is responsible for misincorporation when only G is present.

NASA Discipline Number 52-20↗