Template-directed chemistry and the origins of the RNA world

Kanavarioti, Anastassia

doi:10.1007/bf01582032

Cited by 19 publications

(11 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our finding that this diverse group of guanosine derivatives with such widely differing polymerization efficiencies has all essentially identical affinities to poly(C) is quite remarkable. These observations reaffirm that affinity for the template is a necessary, but not sufficient, criterion for efficient template-directed synthesis (Inoue and Orgel 1982;Kanavarioti 1994). Table 2 reports data that extend up to 7.55 mM poly(C) and 10.08 rnM 2-MeImpG.…”

Section: Spectroscopic Data Obtained For Mixtures Of Poly(c) With Varsupporting

confidence: 53%

Affinity of guanosine derivatives for polycytidylate revisited

1995

Self Cite

View full text Add to dashboard Cite

Evidence is presented for complexation of guanosine 5'-monophosphate 2-methylimidazolide (2-MeImpG) with polycytidylate (poly(C)) at pH 8.0 and 23°C in the presence of 1.0 M NaC1 and 0.2 M MgC12 in water. The association of 2-MeImpG with poly(C) was investigated using UV-vis spectroscopy as well as by monitoring the kinetics of the nucleophilic substitution reaction of the imidazole moiety by amines. The results of both methods are consistent with moderately strong poly(C) • 2-MeImpG complexation and the spectrophotometric measurements allowed the construction of a binding isotherm with a concentration of 2-MeImpG equal to 5.55 + 0.15 n~ at half occupancy. UV spectroscopy was employed to establish the binding of other guanosine derivatives on poly(C). These derivatives are guanosine 5'-monophosphate (5'GMP), guanosine 5'-monophosphate imidazolide (ImpG), and guanosine 5"-monophosphate morpholidate (morpG). Within experimental error these guanosine derivatives exhibit the same affinity for poly(C) as 2-MelmpG.

show abstract

Section: Spectroscopic Data Obtained For Mixtures Of Poly(c) With Varsupporting

confidence: 53%

Affinity of guanosine derivatives for polycytidylate revisited

1995

Self Cite

View full text Add to dashboard Cite

show abstract

“…Previous models of the origin of nucleic acid replication have consisted of ordinary differential equation models that incorporate high-level chemical assumptions (Kanavarioti and Bemasconi 1990;Kanavarioti 1994;Fernando and Di Paolo 2004) such as direct chain growth (Wattis and Coveney 1999), subexponential or parabolic template growth rates in a closed system (Von Kiedrowski 1993), ribozyme effects, or postulate idealized replication mechanisms (Wills et al 1998). Macroscopic physical models of template replication, although ingeniously relaxing these assumptions, do not embody the order of magnitude differences in rates between phosphoamidatebond (p-bond) and Watson-Crick base-pair (h-bond) events observed in nucleic acids, and have not yet demonstrated long template replication (Breivik 2001;Griffith et al 2005).…”

Section: Introductionmentioning

confidence: 99%

A Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators

2007

View full text Add to dashboard Cite

Abstract. The origin of nucleic acid template replication is a major unsolved problem in science. A novel stochastic model of nucleic acid chemistry was developed to allow rapid prototyping of chemical experiments designed to discover sufficient conditions for template replication. Experiments using the model brought to attention a robust property of nucleic acid template populations, the tendency for elongation to outcompete replication. Externally imposed denaturation-renaturation cycles did not reverse this tendency. For example, it has been proposed that fast tidal cycling could establish a TCR (tidal chain reaction) analogous to a PCR (polymerase chain reaction) acting on nucleic acid polymers, allowing their self-replication. However, elongating side-reactions that would have been prevented by the polymerase in the PCR still occurred in the simulation of the TCR. The same finding was found with temperature and monomer cycles. We propose that if cycling reactors are to allow template replication, oligonucleotide phenotypes that are capable of favorably altering the flux ratio between replication and elongation, for example, by facilitating sequence-specific cleavage within templates, are necessary; accordingly the minimal replicase ribozyme may have possessed restriction functionality.

show abstract

“…Despite the many attractive features of the RNA world hypothesis (Gilbert 1986), the links between prebiotic chemistry and the RNA world have not been convincingly demonstrated (Joyce 1987;Joyce and Orgel 1993;Ferris 1994;Kanavarioti 1994;Orgel 1995;James and Ellington 1995). In most cases, nonenzymatic, templatedirected chemistry using RNA or RNA-like templates has faithfully directed the synthesis of the complementary strand (Joyce 1987;Joyce and Orgel 1993).…”

Section: Introductionmentioning

confidence: 99%

Preference for Internucleotide Linkages as a Function of the Number of Constituents in a Mixture

Kanavarioti

1998

J Mol Evol

Self Cite

View full text Add to dashboard Cite

Phosphoimidazolide-activated ribomononucleotides (*pN; see Scheme I) are useful substrates for the nonenzymatic synthesis of oligonucleotides. In the presence of metal ions dilute neutral aqueous solutions of *pN (0.01 M) typically yield only small amounts of dimers and traces of oligomers; most of *pN hydrolyzes to yield nucleoside 5'-monophosphate (5'NMP). An earlier investigation of *pN reactions in highly concentrated aqueous solutions (up to 1.4 M) showed, as expected, that the percentage yield of the condensation products increases and the yield of the hydrolysis product correspondingly decreases with *pN concentration (Kanavarioti 1997). Here we report product distributions in reactions with one, two, or three reactive components at the same total nucleotide concentration. *pN used as substrates were the nucleoside 5'-phosphate 2-methylimidazolides, 2-MeImpN, with N = cytidine (C), uridine (U), or guanosine (G). Reactions were conducted as self-condensations, i. e., one nucleotide only, with two components in the three binary U,C, U,G, and C,G mixtures, and with three components in the ternary U,C, G mixture. The products are 5'NMP, 5',5'-pyrophosphate-, 2',5'-, 3', 5'-linked dimers, cyclic dimers, and a small percentage of longer oligomers. The surprising finding was that, under identical conditions, including the same total monomer concentration, the product distribution differs substantially from one reaction to another, most likely due to changing intermolecular interactions depending on the constituents. Even more unexpected was the observed trend according to which reactions of the U,C,G mixture produce the highest yield of internucleotide-linked dimers, whereas the self-condensations produce the least and the reactions with the binary mixtures produce yields that fall in between. What is remarkable is that the approximately two-fold increase in the percentage yield of internucleotide-linked dimers is not due to a concentration effect or a catalyst, but to the increased complexity of the system from a single to two and three components. These observations, perhaps, provide an example of how increased complexity in relatively simple chemical systems leads to organization of the material and consequently to chemical evolution. A possible link between prebiotic chemistry and the postulated RNA world is discussed.

show abstract

Template-directed chemistry and the origins of the RNA world

Cited by 19 publications

References 54 publications

Affinity of guanosine derivatives for polycytidylate revisited

Affinity of guanosine derivatives for polycytidylate revisited

A Stochastic Model of Nonenzymatic Nucleic Acid Replication: “Elongators” Sequester Replicators

Preference for Internucleotide Linkages as a Function of the Number of Constituents in a Mixture

Contact Info

Product

Resources

About