Achiral, acyclic nucleic acids: synthesis and biophysical studies of a possible prebiotic polymer

Abstract

The search for prebiotic, nucleic acid precursors is, at its best, a speculative undertaking. Given the complex structure of RNA, it is not very likely that RNA was the first information system in the universe and thus finding possible precursor/s i.e. pre-RNA remains an open challenge. We, in this paper, have tried to construct nucleic acid polymers with a simple acyclic, achiral backbone. Such a linear, achiral backbone may have been formed from simple monomers that may have existed in the "prebiotic soup". We have shown that such polymers are capable of identifying the complementary "other self" and thus forming a potential system for information storage and transmission. This study thus involves investigation of nucleic acid analogues with a modified backbone that are likely to have formed in the prebiotic setting.

Enzymatic Incorporation of Modified Purine Nucleotides in DNA

“…Notably, TIPP (a pyrophosphatase) was included in all reaction mixtures before adding the primer template. We previously observed that adding TIPP prevented pyrophosphate (PP i )‐induced template and/or primer degradation (pyrophosphorolysis) . This process could even occur with 3′→5′ exonuclease‐deficient DNA polymerases to generate new deoxynucleotide triphosphates (dNTPs), which would lead to incorrect incorporation of monophosphates (MPs) .…”

Design and Hybridization Properties of Acyclic Xeno Nucleic Acid Oligomers

“…Srivastava et al. designed achiral XNAs as candidates for the prebiotic genetic carrier in pre‐RNA world [24] . Diethanol amide nucleic acid (DEANA) has an achiral scaffold of eight main chain atoms, which is two atoms longer than natural systems (Figure 3).…”

“…Triethanol amino nucleic acid (TEANA) has also been synthesized (Figure 3). TEANA has an ethyl group as an internal linker between nucleobase and nitrogen in the backbone [24] . TEANA oligomers have not yet been evaluated.…”

Customizable and Regioselective One‐Pot N−H Functionalization of DNA Nucleobases to Create a Library of Nucleobase Derivatives for Biomedical Applications

“…The synthesis of N-alkylated A followed previously reported synthetic procedures. [16,33,40] Briefly, A was treated with potassium carbonate (K 2 CO 3 ) in anhydrous N,N-dimethylformamide (DMF), followed by the addition of 1,2-dibromoethane 2 at room temperature (r.t.) to obtain 9-(2-bromoethyl)-9H-purin-6amine 1 in moderate yield (53 %). A was also treated with 1,3dibromopropane 4 to generate the 9-(3-bromopropyl)-9Hpurin-6-amine 3 in good yield (77 %) (Scheme 1), following a similar synthetic procedure.…”

“…Some successful examples of T N-alkylations have been reported in the literature. [27,40,44] Following similar conditions to those reported in the literature, although using different alkylating agents, namely 1,2-dibromoethane 2 and 1,3-dibromopropane 4, different reaction conditions were tested such as the use of phase transfer catalysts (PTC), solvents [water, dichloromethane, anhydrous DMF, dimethyl sulfoxide (DMSO), and tetrahydrofuran (THF)], bases (K 2 CO 3 , NaOH and NaH), as well as distinct heating methods [conventional, microwave (MW) and ohmic heating]. However, in most of the cases no reaction occurred, or the expected N-alkylated T was not obtained.…”