Nucleic acid sequencing backbone

The amino acid sequence of our first aPNA (which we termed backbone 1 or bl) was designed based on this amphipathic hehx sequence (Fig. 5.3 B). Specifically, this aPNA backbone included hydrophobic amino acids (Ala and Aib), internal salt bridges (Glu-(aa)3-Lys-(aa)3-Glu), a macrodipole (Asp-(aa)i5-Lys), and an N-ace-tyl cap to favor a-helix formation. The C-termini of these aPNA modules end in a carboxamide function to preclude any potential intramolecular end effects. Each aPNA module incorporates five nucleobases for Watson-Crick base pairing to a target nucleic acid sequence. 

The particular sequence of side chains or amino acids along the polypeptide backbone is known as the primary structure. This structure is determined by a particular sequence of nucleic acids in the gene the relationship between a nucleic acid sequence and an amino acid sequence is known as the genetic code (see section 3.2). 

When two nucleic acid strands have complementary nucleic acid sequence, they can undergo hybridization to form double-stranded duplex structures. DNA forms a double-stranded helix composed of two complementary helical polynucleotide chains, aligned antiparallel, which are coiled around a common axis. In helix form, the anionic backbone lies on the outside of the structure with the nucleobases in the core, perpendicular to the axis and separated by a distance of 3.4 A. This B-form helix (Figure 2a) has a right-handed coil that repeats itself every 34 A with a turn every... 

Most reactions of nucleic acid hydrolysis break bonds in the polynucleotide backbone. Such reactions are important because they can be used to manipulate these polymeric molecules. For example, hydrolysis of polynucleotides generates smaller fragments whose nucleotide sequence can be more easily determined. 

A nucleic acid polymer contains nucleotide chains in which the phosphate group of one nucleotide links to the sugar ring of a second. The resulting backbone is an alternating sequence of sugars and phosphates, as shown in... 

Three classes of nucleic acid triple helices have been described for oligonucleotides containing only natural units. They differ according to the base sequences and the relative orientation of the phosphate-deoxyribose backbone of the third strand. All the three classes involve Hoogsteen or reverse Hoogsteen-like hydrogen bonding interaction between the triple helix form-... 

RNAi technology has obvious therapeutic potential as an antisense agent, and initial therapeutic targets of RNAi include viral infection, neurological diseases and cancer therapy. The synthesis of dsRNA displaying the desired nucleotide sequence is straightforward. However, as in the case of additional nucleic-acid-based therapeutic approaches, major technical hurdles remain to be overcome before RNAi becomes a therapeutic reality. Naked unmodified siRNAs for example display a serum half-life of less than 1 min, due to serum nuclease degradation. Approaches to improve the RNAi pharmacokinetic profile include chemical modification of the nucleotide backbone, to render it nuclease resistant, and the use of viral or non-viral vectors, to achieve safe product delivery to cells. As such, the jury remains out in terms of the development and approval of RNAi-based medicines, in the short to medium term at least. 

This approach was the first application of non-enediyne carbon centered radical mediated DNA cleavage agents that were not only capable of binding to DNA but could also be sequence specific. Further work is still needed to elucidate and confirm the sites of cleavage, nature of binding of these molecules and the mechanism of hydrogen abstraction from the nucleic acid backbone. 

The backbone of nucleic acids is connected through the 3 and 5 sites on the sugar with the base attached at the 1 site. Because the sugar molecule is not symmetrical each unit can be connected differently, but there is order (also called sense or directionality) in the sequence of... 

The primary structure of nucleic acids refers to the sequence in which the four nitrogen bases (A, G, C and T in DNA and A, G, C and U) in RNA are attached to sugar phosphate backbone of the nucleotide chain. 

Just as the structure of a protein depends on its sequence of individual amino acids, the structure of a nucleic acid depends on its sequence of individual nucleotides. To carry the analogy further, just as a protein has a polyamide backbone with different side chains attached to it, a nucleic acid has an alternating sugar-phosphate backbone with different amine base side chains attached. 

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