Mapping the Landscape of Potentially Primordial Informational Oligomers: Oligodipeptides and Oligodipeptoids Tagged with Triazines as Recognition Elements

ArticleinAngewandte Chemie International Edition 46(14):2470-7 · March 2007with15 Reads
DOI: 10.1002/anie.200603207 · Source: PubMed
Abstract
(Chemical Equation Presented) Pairing up: Oligodipeptide, oligodeoxy-dipeptide, or oligodipeptoid backbones tagged with the 2,4-diaminotriazine nucleus pair strongly with complementary DNA and RNA. This is in sharp contrast with the behavior of the 2,4-dioxotriazine nucleus, which does not act as a nucleo-base in these systems.
    • "There are many structures that have required complicated synthesis, have failed to show stable basepairing (though not necessarily isomers of the single formula considered herein), and nevertheless have been reported in the literature, dating back at least 40 years. Some examples include FNA (Schneider and Benner, 1990b), which has since been found to be a more stable base-pairing structure than was originally believed (Zhang et al., 2010); various S-linked riboside polymers, which were found to be poor base-pairing systems (Schneider and Benner, 1990a ); amino acid backbone systems (Buttrey et al., 1975 ); and systems using unusual bases (Mittapalli et al., 2007). It remains a matter of speculation whether the molecular structures involved in contemporary biochemistry are FIG. "
    [Show abstract] [Hide abstract] ABSTRACT: Ribonucleic acid (RNA) is one of the two nucleic acids used by extant biochemistry and plays a central role as the intermediary carrier of genetic information in transcription and translation. If RNA was involved in the origin of life, it should have a facile prebiotic synthesis. A wide variety of such syntheses have been explored. However, to date no one-pot reaction has been shown capable of yielding RNA monomers from likely prebiotically abundant starting materials, though this does not rule out the possibility that simpler, more easily prebiotically accessible nucleic acids may have preceded RNA. Given structural constraints, such as the ability to form complementary base pairs and a linear covalent polymer, a variety of structural isomers of RNA could potentially function as genetic platforms. By using structure-generation software, all the potential structural isomers of the ribosides (BC5H9O4, where B is nucleobase), as well as a set of simpler minimal analogues derived from them, that can potentially serve as monomeric building blocks of nucleic acid-like molecules are enumerated. Molecules are selected based on their likely stability under biochemically relevant conditions (e.g., moderate pH and temperature) and the presence of at least two functional groups allowing the monomers to be incorporated into linear polymers. The resulting structures are then evaluated by using molecular descriptors typically applied in quantitative structure-property relationship (QSPR) studies and predicted physicochemical properties. Several databases have been queried to determine whether any of the computed isomers had been synthesized previously. Very few of the molecules that emerge from this structure set have been previously described. We conclude that ribonucleosides may have competed with a multitude of alternative structures whose potential proto-biochemical roles and abiotic syntheses remain to be explored.
    Full-text · Article · Jul 2015
    • "The same reaction performed at room temperature afforded glycine, parabanic acid, hydantoin and hydantoin derivatives as the only recovered products (spark discharge performed under an inert argon atmosphere only yielded triazines). Triazines are prebiotically relevant, since these compounds embedded in peptidic oligomers can establish strong interactions with nucleobases [82] [83]. The authors suggested a reaction pathway involving the formation of cyanoacetylene and cyanoacetaldehyde for the synthesis of cytosine and uracil, while triazines were most probably obtained by a sequence of urea transformations with biuret (aminocarbonyl urea) and isocyanic acid HCNO as key intermediates [84]. "
    [Show abstract] [Hide abstract] ABSTRACT: The presence of organic molecules in meteorites clearly indicates the occurrence of a large panel of chemical reactions in space conditions. The scenarios in which these transformations take place are diverse and fascinating: proto-stellar nebulae, dense or rarefied clouds of interstellar and cosmic dust particles, comets, meteorites, proto-planets and asteroids. High energy particles (cosmic rays and solar winds), heat, electromagnetic radiations, and radioactive decays continuously interact with simple chemical precursors to yield new complex derivatives. Some of these reactions are more relevant than others in the process of origin of life. The prebiotic chemistry in space conditions finally determines the synthesis of molecules that may play a key role in the organization of the first genetic and metabolic systems. Once synthesized some molecules can be transported through the universe until habitable planets. The description of the full set of these reactions is extremely complex and necessarily incomplete. In this review, some relevant prebiotic processes in space conditions are described with particular attention to the catalytic role played by stellar objects in the transformation of ubiquitous chemical precursors, such as formamide, formaldehyde and hydrogen cyanide. Thus, amino acids, nucleobases, sugars, lipids and carboxylic acids emerge as very easily synthesizable molecules in the universe ready to join in the first living cell.
    Article · Jun 2015
    • "The most radical proposal for a pre-RNA backbone is, arguably , the peptide nucleic acid (PNA) (Nielsen, 2007). In support of this proposal, albeit with a structure distinct from the classic PNA, glutamate and aspartate (22 and 23;Figure 1B) have been used to replace both ribose and phosphate to form a different type of peptide nucleic acid backbone (Mittapalli et al., 2007aMittapalli et al., , 2007b). Specifically, a peptide of repeating aspartic acid (or glutamic acid) residues can serve as a nucleic acid backbone with alternating residues that act as either an IL or a TC, with the latter moiety-possessing RUs conjugated to amino acid side chains. "
    [Show abstract] [Hide abstract] ABSTRACT: The origin of RNA is one of the most formidable problems facing prebiotic chemists. We consider RNA as a product of evolution, as opposed to the more conventional view of RNA as originally being the product of abiotic processes. We have come to accept that life's informational polymers have changed in chemical structure since their emergence, which presents a quandary similar to the paradox of "My Grandfather's Axe". Here, we discuss reasons why all contemporary components of RNA-the nucleobases, ribose, and phosphate-are not likely the original components of the first informational polymer(s) of life. We also evaluate three distinct models put forth as pathways for how the earliest informational polymers might have assembled. We see the quest to uncover the ancestors of RNA as an exciting scientific journey, one that is already providing additional chemical constraints on the origin of life and one that has the potential to produce self-assembling materials, novel catalysis, and bioactive compounds.
    Full-text · Article · Apr 2013
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