Showing papers by "Leslie E. Orgel published in 1996"

Synthesis of long prebiotic oligomers on mineral surfaces

Abstract: Most theories of the origin of biological organization assume that polymers with lengths in the range of 30-60 monomers are needed to make a genetic system viable. But it has not proved possible to synthesize plausibly prebiotic polymers this long by condensation in aqueous solution, because hydrolysis competes with polymerization. The potential of mineral surfaces to facilitate prebiotic polymerization was pointed out long ago. Here we describe a system that models prebiotic polymerization by the oligomerization of activated monomers -both nucleotides and amino acids. We find that whereas the reactions in solution produce only short oligomers (the longest typically being a 10-mer), the presence of mineral surfaces (montmorillonite for nucleotides, illite and hydroxylapatite for amino adds) induces the formation of oligomers up to 55 monomers long. These are formed by successive "feedings" with the monomers; polymerization takes place on the mineral surfaces in a manner akin to solid-phase synthesis of biopolymers.

Catalysis of the Oligomerization of O-Phospho-Serine, Aspartic Acid, or Glutamic Acid by Cationic Micelles

Abstract: Treatment of relatively concentrated aqueous solutions of O-phospho-serine (50 mM), aspartic acid (100 mM) or glutamic acid (100 mM) with carbonyldiimidazole leads to the formation of an activated intermediate that oligomerizes efficiently. When the concentration of amino acid is reduced tenfold, few long oligomers can be detected. Positively-charged cetyltrimethyl ammonium bromide micelles concentrate the negatively-charged activated intermediates of the amino acids at their surfaces and catalyze efficient oligomerization even from dilute solutions.

Phosphorylation of glyceric acid in aqueous solution using trimetaphosphate.

Abstract: The phosphorylation of glyceric acid is an interesting prebiotic reaction because it converts a simple, potentially prebiotic organic molecule into phosphate derivatives that are central to carbohydrate metabolism. We find that 0.05 M glyceric acid in the presence of 0.5 M trimetaphosphate in alkaline solution gives a mixture of 2- and 3-phosphoglyceric acids in combined yields of up to 40%.

Oligomerization of negatively-charged amino acids by carbonyldiimidazole.

Abstract: The carbonyldiimidazole-induced oligomerizations of aspartic acid, glutamic acid and O-phospho-serine are amongst the most efficient reported syntheses of biopolymers in aqueous solution. The dependence of the yields of products on the concentrations of reagents, the temperature and the enantiomeric composition of the substrate amino acids are reported. Catalysis by metal ions, particularly by Mg2+, is described. These reactions do not generate significant amounts of material in the size-range of several tens of residues that are thought to be needed for a polymer to function as a genetic material.

Polymerization of amino acids

Abstract: One of the central problems of the origin of life is the prebiotic synthesis of long biopolymers in aqueous solution. We are studying the polymerization of aand [~-amino acids with negatively charged side chain using a water-soluble carbodiimide, N-(3-Dimethylaminopropyl)-Nethylcarbodiimide hydrochloride (EDAC) or carbonyldiimidazole (CDI) as condensing agent. We find that a-amino acids can be polymerized efficiently using CDI, whereas I~-amino acids are best polymerized using EDAC. In the CDI reaction, the elongation of oligopeptides is enantioselective. The enantiomer with the same chirality as that of the primer is preferred in the extension of homo-chiral L-glulo. Cyanamide, like EDAC, can be used to polymerize [~-amino acids if the reaction is carded out at high temperature and low pH. By using transition metal ions as catalysts, the reaction may be performed successfully at pH5-6. In the presence of bicarbonate, a-thioglutamic acid oligomerizes satisfactorily. More interestingly, some minerals such as ferrous sulfide or illite, catalyze the polymerization efficiently. Utilizing \"feeding\" techniques, we can synthesize high molecular weight poly [3-peptides on the surface of positively charged minerals, such as hydroxylapatite, using EDAC as condensing agent. Preliminary results show that these polypeptides are branched (dendrimers) rather than linear polymers. Long a-peptides can be obtained by ligating short oligomers such as L-glu3 on the surface of hydroxylapatite using EDAC as condensing agent.

PNAs — A prebiotic template? enantiomeric cross-inhibition on the nonchiral template and the rearrangement of peptide nucleic acids in aqueous solution

Abstract: Prebiotic syntheses of potentially chiral monomers always yield racemic mixtures. Living systems, however, utilize L-aminoacids and D-nucleotides in their biopolymers. The generation of optical asymmetry by selection and amplification in an autocatalytic process is, therefore, an important element in many theories of the origin of life (Ponnamperuma and Chela-Flores, 1992; Wald, 1957). Replication of polynucleotides in template-directed syntheses is an obvious candidate for such an amplification step in a pre\"RNA world\" (Gesteland and Atkins, 1993). A serious objection to this suggestion is the observation that the efficiency of template-directed syntheses of RNA is limited by enantiomeric cross-inhibition (Joyce et al., 1984). Peptide Nucleic Acids (PNAs) (Egholm et al., 1993; Nielsen et al., 1991; Wittung et al., 1994), amide-linked, nonchiral analogs of RNA, have been copied into RNA non-enzymatically (BShler et al., 1995) and constitute an alternative to chiral polynucleotides as an informational replicating system. We used PNA as model for a hypothetical, non-chiral precursor of RNA in experiments \"revisiting chiral selection\". We found that enantiomeric cross-inhibition is as serious in the polymerization of nucleotides on a PNA template as it is on a conventional DNA template. However, experiments on the elongation of a nucleic acid primer on a DNA or on a PNA template lead to the formation of predominantly homochiral adducts. This suggests that enantiomeric cross-inhibition may be a less severe obstacle to replication than was previously thought. To act as a prebiotic template, PNA's would have to be stable under prebiotic conditions. Our experiments on the rearrangement and hydrolysis of PNAs, however, show that they rearrange relatively rapidly. This makes it questionable that PNAs themselves were important prebiotic molecules.