Nucleotide and Nucleic Acid Modifications

Section IV describes the structures and functions of the nucleotides and nucleic acids, and covers many major topics such as DNA replication and repair, RNA synthesis and modification, and protein synthesis. It also discusses new findings on how genes are regulated and presents the principles of recombinant DNA technology. 

Modifications of Nucleosides, Nucleotides, and Nucleic Acids using Huisgen s [3+2] Azide-Alkyne Cycloaddition ... 

Metal ions are usually required to promote and stabilize functionally active or native conformations of nucleic acids, as well as to mediate nucleic acid-protein interactions. However, metal ions can also cause structural transformation of nncleic acids, or denature their native structures. In addition to structural roles, some metal compounds can indnce cleavage (i.e. scission, fragmentation, or depolymerization) and modification (withont cleavage) of nucleic acids. Metal-nucleic acid interactions can be either nonspecific or dependent on the chemical nature of nucleotide residues, nucleic acid sequence, or secondary and/or tertiary structure of nucleic acids. The specificity of these interactions is dependent... 

Succinylated derivatives of nucleic acids may be prepared by reaction of the anhydride with available —OH groups. The reaction forms relatively stable ester derivatives that create car-boxylates on the nucleotide for further conjugation or modification (Figure 1.83). This method has been used in nucleic acid synthesis (Matteucci and Caruthers, 1980) and to derivatize nucleotide analogs such as AZT (Tadayoni et al., 1993). 

Metz, D.H., and Brown, G.L. (1969) The investigation of nucleic acid secondary structure by means of chemical modification with a carbodiimide reagent. I. The reaction between N-cyclohexyl-N -b-(4-methylmorpholinium)ethyl carbodiimide and model nucleotides. Biochemistry 8, 2312-2328. 

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. 

In photobiology these negative actions start with the processes which modify or destroy the essential molecules of life, specifically the nucleic acids and the proteins. The former carry the genetic code in a sequence of nucleotides and even a minor modification of the nucleotide sequence can have profound consequences. By the laws of chance alone these modifications and their consequences are almost always detrimental and result usually in the death of the organism (e.g. microbes) exposed to short-wavelength ultraviolet radiation. 

N. K. Kochetkov, Chemical modification of nucleotides and its application to the investigation of nucleic acid structure, Pure Appl. Chem., 18 (1969) 257-273. 

Among fluorescence probes of nucleic acid structure, dynamics, and folding, 2-aminopurine (2AP) is unique in that its introduction into an RNA can often be done with little perturbation of the RNA structure. Whereas other fluorescent nucleotide analogs have higher quantum yields than 2AP, their modifications have the potential to disrupt secondary and... 

---