Linked nucleic acids,

Nucleic acids have been linked to a variety of surfaces including polystyrene beads, glass, silicon, gold, and even cells. Immobilization of nucleic acids may occur through a number of covalent linkages that are the subject of other chapters. Strept(avidin) may then be bound to a surface through a biotinylated nucleic acid linker. Alternatively, strept(avidin) may be linked to a surface directly with methods used for other proteins. This chapter will describe the biotin-strept(avidin) system and focus on the use of the biotin-strept(avidin) to link nucleic acids to surfaces. 

Fig. 1 Modified nucleic acids with enhanced nuclease stability, a DNA, b phosphorothioate, c Z -OjT-C-methylene-bridged (locked) nucleic acid (LNA), d 2f-0,A -C-ethylene-bridged nucleic acid (ENA), e Z -O-methyl nucleic acid, f methylphosphonate-linked nucleic acid, g morpholino-linked nucleic acid, h peptide nucleic acid (PNA)...

It has been demonstrated that the tran5 -[(NH3)2PtCl] adduct of 1-methylcytosine, bound via N-3, can form crosslinks with either 9-ethylguanine or 9-methyladenine as a result of Cl substitution by purine N-7 atoms. Additional H-bonds between exocyclic groups of cross-linked nucleic acid bases provide additional stabihzation of the individual complexes (Figure 13d). Binding of the related complex [(NH3)2Pt(N-3-cytosine)Cl]+ with d(GG) leads to the formation of a major product in which the platinum is bound only to N-7 of the 5 -nucleotide. ... 

Edfeldt NB, Harwood EA, Sigurdsson ST, Hopkins PB, Reid BR. Solution structure of a nitrous acid-induced DNA interstrand DNA cross-link. Nucleic Acids Res. 2204 32 2785-2794. 

Antibodies to nucleic acids have found many uses in the specific measurement of naturally occurring or modified nucleic acids both in solution and in situ. To obtain the required antibodies, it has been necessary to link nucleic acids or their components to carrier proteins or synthetic polypeptides to form immunizing complexes because injection of purified nucleic acids alone into normal animals does not stimulate significant antibody production. Once the antibodies are formed, they react with the nucleic acid in the absence of carrier. 

Cross-linking psoralen cross-links nucleic acid under UV irradiation specific for ds nucleic acid (purity not a necessity) gapped probes (with ss in sert) possible good detectability... 

Figure 2.10 Methylphosphonate and Linked Nucleic Acids. Oligo-/p°lynucleotide or oligo-/polydeo-xynucLeotide (as shown) methylphosphonates (left) have chiral properties in common with phospho-rothioates. However lack of charge on the phosphonodiester backbone results in quite significantly more hydrophobic biophysical characteristics. Locked nucleic acids (LNAs) (right) are now the subject of great interest since very stable RNA A-helices may be formed between wild-type RNA and base-complementary NAs.

The most direct way to link nucleic acids to carbon nanotubes is simply by sonicating an aqueous solution of the nucleic acid with the carbon nanotubes (Fig. 18.4). In 2003, Zheng et al. 

The most common strategy for non-covalently linking nucleic acids to carbon nanotubes is through electrostatic attraction between alkylammonium ions covalently appended to the carbon... 

As the result of our kinetic evidence, we had to propose a mechanism (Scheme 2) for the process of RNA cleavage by imidazole buffer, and other buffers such as morpholine, in which the first function of the BIP" is to protonate the phosphate group. We have proposed [2] that the enzyme ribonuclease A uses a related mechanism (Scheme 3)— but simultaneous instead of sequential—and cited some physical and calculational evidence in support of this proposal. We have used the evidence from this mechanistic work to redesign a catalyst that imitates some aspects of the enzyme mechanism. However, we were also forced to think about the properties of the isomeric 2, 5 -linked nucleic acids whose formation was a key piece of evidence in the mechanistic studies. We will first describe work fliat addresses this question. 

DNA stands for deoxyribonucleic acid. It is the biological blueprint of life. DNA is made up of a double-stranded structure consisting of sugar (deoxyribose) and phosphate back bone, cross linked with two types of nucleic acids referred to as purines (adenine and guanine) and pyrimidines (thymine and cytosine) (Fig. 1). The cross linking nucleic acids always pair a purine with a pyrimidine, such that adenine always pairs with thymine and guanine always pairs with cytosine. 

Both L- and D-ribose occur in this complex mixture, but are not particularly abundant. Since all carbohydrates have somewhat similar chemical properties, it is difficult to envision simple mechanisms that could lead to the enrichment of ribose from this mixture, or how the relative yield of ribose required for the formation of RNA could be enhanced. However, the recognition that the biosynthesis of sugars leads not to the formation of free carbohydrates but of sugar phosphates, lead Albert Eschenmoser and his associates to show that under slightly basic conditions the condensation of glycoaldehyde-2-phosphate in the presence of formaldehyde considerable selectivity exist in the synthesis of ribose-2,4-diphosphate 54). This reaction has also been shown to take place under neutral conditions and low concentrations in the presence of minerals (55), and is particularly attractive given the properties of pyranosyl-RNA (p-RNA), a 2 ,4 -linked nucleic acid analogue whose backbone includes the six-member pyranose form of ribose-2,4-diphosphate 56). 

Abbas S, Hayes CJ. An improved procedure for the s3mthesis of vinylphosphonate-linked nucleic acids. Tetrahedron Lett. 2000 41 4513 517. 

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