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

Mittapalli, Gopi Kumar; Reddy, Kongara Ravinder; Xiong, Hui; Munoz, Omar; Han, Baozhong; Riccardis, Francesco De; Krishnamurthy, Ramanarayanan; Eschenmoser, Albert

doi:10.1002/ange.200603207

Cited by 27 publications

(20 citation statements)

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“…In the present study, neither the catalyst nor the reaction conditions are conventionally prebiotic, and the replication does not involve an "informational" oligomer though such synthetic structures do exist and are capable of information transfer and pairing with RNA (22,23). There are also synthetic cyclic phosphates embedded in chiral microenvironments that feature the same functional group as the phosphodiesters of RNA and DNA.…”

Section: Resultsmentioning

confidence: 88%

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

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The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of selfreplication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to α,β-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.imidazolidinone catalysis | self-replication | template effects S tudies of prebiotic chemistry raise questions concerning which functions came nearer the origin of life-genetics or metabolism (1). The discovery of the catalytic activity of ribozymes provided an answer in which both functions could be accounted for in an "RNA world" (2). Although no one doubted that RNA could carry genetic information, some 15 years lapsed before an RNA molecule was shown to self-replicate (3), and this type of catalysis has since been developed to an extraordinary level of efficiency (4). Short, self-complementary DNA strands were shown to selfreplicate in 1986 (5), and autocatalysis based on molecular recognition was found in simplified organic molecules (6) and even peptides (7). At the present time, many types of self-replicating structures are known (8). These systems function like their nucleic acid counterparts in that the self-complementary structures operate as templates for their own formation. However, unlike ribozymes, the synthetic self-replicating systems are not known to catalyze other chemical reactions. The wholly synthetic structures act as either organocatalysts or autocatalysts, but published evidence for both activities in a single molecule is limited (9). This research was undertaken to find molecules that could perform in both capacities, and we report here an imidazolidinone-based compound and its properties as a catalyst and autocatalyst. Results and DiscussionTo realize an autocatalytic/organocatalytic molecule, we made modifications in the structure of compound 1, a molecule that bears self-complementary hydrogen-bonding subunits-a diaminotriazine and cyclic imide-that allow for dimerization in noncompeting organic media (Fig. 1). The arrangement of these subunits in 1 was earlier shown to allow its action as an autocatalyst (10): It acts as a template for its own synthesis, gathering two subunits on its surface to facilitate the formation of the amide bond. The insertion of a functional group known to catalyze organic transformations into 1 was a prospect to be explored. We initially inserted a thiourea into the framework of 1 (11). Although the thiourea function is a widely used organocatalyst (12), its applications were limited in the present context: The same hydrogen bonding that accounts for the thiourea's activity requires the use of solvents that also lead to tight dimerization of the template. This effect minimizes the fraction of the monomeric compound t...

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Section: Resultsmentioning

confidence: 88%

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Most of the nonnatural base pairs studied thus far have maintained the form of a base comprised of a six-membered ring (like a pyrimidine) paired with a base comprised of fused five-and six-membered rings (like a purine), which can be accommodated in a helix also containing canonical WatsonCrick base pairs. However, duplexes that contain all noncanonical base pairs have also been shown, including duplexes with only purinepurine base pairs (Groebke et al 1998;Battersby et al 2007;Heuberger and Switzer 2008b;Engelhart et al 2009), pyrimidine-pyrimidine base pairs (Mittapalli et al 2007a;Mittapalli et al 2007b), and even duplexes with tricyclic bases (Krueger et al 2007). …”

Section: Recent Resultsmentioning

confidence: 99%

“…The use of non-purine or pyrimidine heterocycles may not be so problematic from a prebiotic standpoint. Although purines are abundant in model reactions of the prebiotic chemical inventory using, for instance, formamide and HCN, other, helix-compatible parent heterocycles were surely present in the prebiotic chemical inventory (Mittapalli et al 2007a;Mittapalli et al 2007b), and these should be considered. With respect to C-nucleosides, although they are well-known, they have been less well-examined from a prebiotic standpoint than the canonical N,O-acetal linked nucleosides.…”

Section: Recent Resultsmentioning

confidence: 99%

“…Some Possible Constraints to Guide the Search for Proto-RNA Synthetic chemists have prepared numerous nucleic acid analogs, some as part of origin of life studies (Schneider and Benner 1990;Pitsch et al 1993;Herdewijn 2001b;Benner 2004;Mittapalli et al 2007a;Mittapalli et al 2007b) and many as part of a widespread search for therapeutic agents (Kurreck 2003). These analogs have included changes to both the nucleobases and to the polymer backbone.…”

mentioning

confidence: 99%

“…With regard to origin of life investigations, some proposals for the difference between RNA and an earlier proto-RNA have been subtle, such as the proposal that hypoxanthine once functioned in the place of guanine (these nucleobases differ by only a single exocyclic amino group) (Crick 1968). Other proposals are much more radical, such as the suggestion that the nucleobases were once connected by a completely different and uncharged backbone, as in the synthetic polymer known as peptide nucleic acid (Nelson et al 2000), and intermediate proposals, in which the backbone was a peptide, but still negatively charged (Mittapalli et al 2007a;Mittapalli et al 2007b) (Fig. 2).…”

mentioning

confidence: 99%

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