Biologically important compounds nucleotides

An important class of naturally occurring anions are the nucleoside phosphates (i.e. nucleotides) present in nucleic acids, sugar nucleotides for glycosylation of oligosaccharides or proteins, activated forms of proteins and chemical mediators which play a central role in intracellular signals. Artificial phosphate receptors allow for detection and separation of biologically important compounds. However, most chemical receptors are soluble in solution and cannot be therefore separated easily from the solution binding the desired compound. 

As important as nucleotides of adenosine are to bioenergetics that is not the only indispensable part they play m biology The remainder of this chapter describes how these and related nucleotides are the key compounds m storing and expressing genetic information... 

Owing to the great biological importance of this class of compounds, the 13C NMR spectra of a considerable number of nucleosides and nucleotides and their aglycones have been reported in the literature [147,428, 460, 676, 735, 748-760]. As demonstrated by the spectra of flavin adenine dinucleotide (Fig. 5.9), the 13C NMR spectra of nucleosides and nucleotides have two groups of signals ... 

It was found that the polymer exhibited selectivity towards phosphomonoester dianions. Less polar compounds were found to bind non-specifically to the polymer. The polymer was then used as a stationary phase for a HPLC column. A mixture containing dA, 5 -dAMP and 3, 5 -cAMP was thus separated. As expected, the retention time of 5 -AMP was larger than those for dA and 3, 5 -cAMP. The same was tme for other nucleotides compared to the corresponding nucleosides. When the Zn2+-free control polymer was used, all compounds were immediately eluted. The possibility to use polymer-anchored recognition units to separate biologically important phosphates was thus proved. 

In neutral and slightly alkaline media, MPO-compound I can react directly with iodides, bromides, chlorides (K16), thiocyanates, Al-acetylmethionine, cysteine, pyridine nucleotides (S20), and phenols (K16), including tyrosine (H14) and thyroid hormones. Some of these reactions have certain biological importance. In extensive studies, Klebanoff el al. investigated the potential function of MPO as an iodide-oxidizing enzyme (K16). It was found that iodide is rapidly oxidized, forming a bactericidal derivative which produces a fall in the number of viable Escherichia coli 10 times more effectively than bromide and 100 times more effectively than chloride, if used as MPO substrates. Extremely low concentrations of iodides and bromides in leukocytes and blood plasma, however, seem to limit the importance of iodide oxidation in bacteria killing mechanisms. 

Nuclear spin polarization can be induced in a variety of biologically important molecules by laser irradiation of solutions in the presence of a dye. Initially we had found that using flavin dyes it is possible to polarize the amino acids tyrosine, histidine and tryptophan, both as free amino acids and as surface residues in proteins (, O. This occurs in cyclic reactions with a high degree of reversibility of the type discussed in the previous section. More recently, we found that the purine nucleotide bases can be polarized similarly (16). It appears that flavins are remarkable in that upon photo-excitation they react reversibly with several classes of compounds such as aromatic phenols, aromatic amines, and secondary and tertiary amines. In all these cases CIDNP can be observed. We shall now discuss the photo-CIDNP spectra of the amino acids in more detail. 

Indicine IV-oxide (169) (Scheme 36) is a clinically important pyrrolizidine alkaloid being used in the treatment of neoplasms. The compound is an attractive drug candidate because it does not have the acute toxicity observed in other pyrrolizidine alkaloids. Indicine IV-oxide apparently demonstrates increased biological activity and toxicity after reduction to the tertiary amine. Duffel and Gillespie (90) demonstrated that horseradish peroxidase catalyzes the reduction of indicine IV-oxide to indicine in an anaerobic reaction requiring a reduced pyridine nucleotide (either NADH or NADPH) and a flavin coenzyme (FMN or FAD). Rat liver microsomes and the 100,000 x g supernatant fraction also catalyze the reduction of the IV-oxide, and cofactor requirements and inhibition characteristics with these enzyme systems are similar to those exhibited by horseradish peroxidase. Sodium azide inhibited the TV-oxide reduction reaction, while aminotriazole did not. With rat liver microsomes, IV-octylamine decreased... 

Over the past years, synthetic base-modified nucleosides and nucleotides have displayed important impact in diverse fields. Their biological properties have found application as antiviral tools against hepatitis virus (HBV), herpes virus (VZV) and human immunodeficiency (HIV).94,95,136 Many of those compounds exhibit antiproliferative, antibiotic and antifungal activities and some have been used as probes for DNA damages96,97,137 as well as in the anti-sense approach and DNA-probe technology with fluorescence properties.99... 

Biomolecules are organic compounds found in biological systems. Many are relatively small, with molecular weights of less than 1000 g/mol. There are four main families of these small molecules—simple sugars, nucleotides, amino acids, and lipids. Many simple biomolecules are used to synthesize larger compounds that have important cellular functions, as shown in Figure 3.9. 

The brain needs the influx of nucleosides because the brain is deficient in de novo nucleotide synthesis (102). Purine and pyrimidine nucleosides are necessary for the synthesis of DNA and RNA, but nucleosides also influence many other biological processes. In addition, nucleosides play an important role in the treatment of diseases, such as cardiac diseases, brain cancers, and infections [parasitic and viral (103)]. Nucleosides are hydrophilic compounds, and the influx and efflux of these compounds is therefore mediated by a number of distinct transporters (104). Nucleoside transporters are membrane-fixed transporters and are classified by their transport mechanisms (e = equilibrative, c = concentrative), their sensitivity to the transport inhibitor nitrobenzylmercaptopurine riboside (NBMPR s = sensitive, i = insensitive), and their substrates. Presently, there are two equilibrative transporters (ENTs es and ei) and six concentrative nucleoside transporters [CNTs cif (concentrative, NBMPR insensitive, broad specificity Nl), cit (concentrative, NBMPR insensitive, common permeant thymidine N2), cib (concentrative, NBMPR insensitive, broad specificity N3), cib (concentrative, MBMPR insensitive, broad specificity N4), cs (concentrative, NBMPR sensitive N5), and csg (concentrative, NBMPR sensitive, accepts guanosine as permeant N6) (104)]. The equilibrative es and ei nucleoside transporters are widely expressed in mammalian cells and are present at cultured endothelial cells and brain capillaries (105). In these cells, the expression of concentrative transporter cit (N2) was demonstrated also. In other parts of the rat brain, ei and es nucleoside transport systems have... 

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