A-form nucleic acids

A-form Nucleic Acids A Basis for Aminoglycoside Selectivity to... 

A-FORM NUCLEIC ACIDS A BASIS FOR AMINOGLYCOSIDE SELECTIVITY TO NON-RNA TARGETS... 

Of those small molecules best able to bind DNA-RNA hybrids, very few have been found. At last count, the number was less than ten. For comparison, the nnmber of molecules known to target duplex DNA is perhaps in the thousands. Few reported attempts have been made to target the unique structure of the DNA-RNA hybrids, and consequently only a handful of molecules have been identified. " " A few years ago, we identified aminoglycosides as the antibiotics most likely to stimnlate groove-based recognition of A-form nucleic acid... 

Robinson, H., Gao, Y. G., Sanishvili, R., Joachimiak, A., and Wang, A. H. J. (2000). Hexahydrated magnesium ions bind in the deep major groove and at the outer mouth of A-form nucleic acid duplexes. Nucleic Acids Res. 28, 1760—1766. 

H.-Y. Mei, The Design and Applications of a Chiral Probe for A-form Nucleic Acids, Ph.D. Thesis, Columbia University (1989). J. M. Kelly, A. B. Tossi,... 

H. Robinson, Y.-G. Gao, R. Sanishvili, A. Joachimiak, and A. H. J. Wang, Nucleic Acids Res., 28,1760 (2000). Hexahydrated Magnesium Ions Bind in the Deep Major Groove and at the Outer Mouth of A-Form Nucleic Acid Duplexes. 

The hypothesis that our biological world built on the DNA-RNA-protein central dogma was preceded by an RNA world in which RNA molecules carried both the genetic information and executed the gene functions (through ribozyme activity) is now widely accepted [130]. However, it is also well recognized that RNA due to its vulnerability to hydrolysis - especially as a result of catalysis by divalent metal ions - would not have been able to evolve in a harsh pre-biotic environment Also the formation of RNA under presumed pre-biotic conditions is extremely inefficient It is not so far-fetched to propose that a peptide nucleic acid-like molecule may have been able to function as a form of pre-biotic genetic material since it... 

Masuko M, Ohtani H, Ebatal K, Shimadzu A (1998) Optimization of excimer-forming two-probe nucleic acid hybridization method with pyrene as a fluorophore. Nucleic Acids Res 26 5409-5416... 

Cytosine, thymine, and uracil are pyrimidines along with adenine and guanine they account for the five nucleic acid bases. Pyrimidines are heterocyclic single-ringed compounds based on the structure of pyrimidine. Cytosine, thymine, and uracil, like adenine and guanine, form nucleosides and nucleotides in RNA and DNA. When the bases combine with ribose, a ribo-nucleoside forms and when it attaches to deoxyribose, a deoxyribosenucleoside is formed. Names of the nucleoside are summarized in Table 29.1. These in turn combine with phospho-ryl groups, in a process called phosphorylation, to form their respective nucleotides that form nucleic acids. The nucleotides can be tri, di, and mono phosphate nucleotides similar to the way in which adenine forms ATP, ADP, and AMP. 

Remarkably, HCN-polymers are efficiently obtained at low temperatures suggesting a plausible cold origin-of-life scenario [63-65]. This latter hypothesis provides a mechanism to account for the concentration of HCN and a more stable environment for the newly formed nucleic acid components. Moreover, HCN is easily concentrated at its eutectic temperature (- 23.4 °C) [66,67] and the production of DAMN was found to be accelerated by lowering the temperature of the reaction medium. A large panel of purine derivatives, adenine 1, hypoxanthine 2, diaminopurine 3, xanthine 4 and guanine 5 was obtained after acidic and alkaline hydrolysis at high temperatures of the HCN-polymer produced in a frozen ammonium cyanide solution at - 78 °C for 27 years (Scheme 6 yields of products are reported... 

The difficulties encountered in the untemplated synthesis of natural nucleic acids is one factor that has prompted many researchers to propose alternatives to RNA as the initial genetic material. For example, a derivative of 3 -aminoguanosine can form untemplated chains of up to 20 bases in length.25 In addition, both cyclic and acyclic nucleotide bisphosphate derivatives polymerize without the aid of a template to form nucleic acids with pyrophosphate linkages between the monomers, rather than the more natural phosphodiester linkages.26-29... 

In polymeric nucleic acids, the Watson-Crick base pairs also have the potential to form additional hydrogen bonds. These will generally be saturated by water of hydration molecules. They are, in fact, necessary for specific recognition of a particular nucleic acid base sequence by a particular protein such as, for example,... 

PCR is a resilient process and does not require highly purified nucleic acid. In practice, however, clinical samples may contain unpredictable amounts of impurities that can inhibit polymerase activity. To ensure reliable amplification, some form of nucleic acid purification is often used. The idiosyncratic nature of PCR inhibitors within clinical specimens requires demonstration that the sample (or preparation of nucleic acid purified from it) will allow amplification. A control nucleic acid sequence, usually different from the target, can be added to the sample (or extract from the sample). Failure to amplify this control indicates that further purification of the sample is required to remove inhibitors of the reaction. 

An additional nucleic acid sequence, a probe, may be included in a reassociation reaction and form double strands with components of the initial DNA. This hybridization reaction is the basis of the Southern and northern blotting techniques used to determine if a known nucleic-acid sequence is present in a mixture of nucleic-acid sequences. 

The RNA world model is not without its difficulties. Foremost among these problems is the exceptional challenge in the prebiotic synthesis of RNA (39-40). Many of the presumed proto-metabolic molecules are easily synthesized in experiments that mimic prebiotic environments. RNA nucleotides, by contrast, have never been synthesized from scratch. Furthermore, even if a prebiotic synthetic pathway to nucleotides could be found, a plausible mechanism to link those nucleotides into an RNA strand has not been demonstrated. It is not obvious how useful catalytic RNA sequences would have formed spontaneously in any prebiotic environment. Perhaps, some scientists speculate, a simpler nucleic acid preceded RNA (41-42). 

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