Artificial nucleosides

The approach developed involving a sugar-derived OZT paves the way to novel type artificial nucleosides as presented in the example below (Scheme 67).20... 

Dondoni, A., Mass , A. Decoration of dihydropyrimidine and dihydropyridine scaffolds with sugars via Biginelli and Hantzsch multicomponent reactions An efficient entry to a collection of artificial nucleosides. Mol. Divers. 2003, 6, 261 -270. 

Development of novel artificial nucleosides for the expansion of triplex-recognition codes 04YGK1026. 

With the N-3 atom of cytidine unprotonated under physiological conditions, bases have been proposed to circumvent this disadvantage 87 [254], 88 [255], 89 and 90 [256].The use of artificial nucleosides with bases such as 4-(3-benzamidophenyl)imidazole, which binds to T A and C G, has also been proposed in triple helix antisense concepts [257]. 

B. Artificial Nucleosides Designed for Metal-Mediated Base Pairs 49... 

Figure 4 Examples of artificial nucleosides in which DNA bases are replaced by ligands for metal ions.

Many of the mutations caused by artificially produced base analogues are transitions. Mutations are produced by base analogues in one of two different ways. On entering the cell, a base analogue is converted to a nucleoside triphosphate that base pairs, perhaps incorrectly, with a DNA template and is inserted into the nucleotide chain. This is one way in which the mutation can be produced. The other requires an additional round of replication so that an improper base pair forms as a result of the previously incorporated analogue. The result in both cases is a permanently modified DNA. 

G-clamp nucleoside analogues 135 are of interest for the generation of artificial nucleotide sequences, as a result of their ability to bind tightly to guanine. Incorporation of these into antisense nucleotides is reported to confer enhanced potency <1999PNA3513>. 

Especially attractive was the possibility to connect nucleosides, as has been realized, for instance, with the hexathymidine 141 and with the elongated and alternating strands 142 and 143. These compounds represent artificial oligonucleosides, which may interact with natural polynucleotides or nucleic acids. On treatment with Cu(i), 142 and 143 gave the double-helical complexes 144 and 145, respectively, inside-out analogues of double-stranded nucleic acids, which may be termed deoxy-... 

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. 

The palladium-catalyzed cross-coupling reaction of organosilicon compounds is applied to the synthesis of biologically active compounds. Some examples are described in the following schemes artificial HMG-CoA reductase inhibitor, NK-104 (Scheme 7) [46-48], a precursor of a DNA topoisomerase inhibitor (Scheme 8) [49] and nucleosides (Eq. 40) [501. 

To establish a correlation between the concentrations of different kinds of nucleosides in a complex metabolic system and normal or abnormal states of human bodies, computer-aided pattern recognition methods are required (15, 16). Different kinds of pattern recognition methods based on multivariate data analysis such as principal component analysis (PCA) (8), partial least squares (16), stepwise discriminant analysis, and canonical discriminant analysis (10, 11) have been reported. Linear discriminant analysis (17, 18) and cluster analysis were also investigated (19,20). Artificial neural network (ANN) is a branch of chemometrics that resolves regression or classification problems. The applications of ANN in separation science and chemistry have been reported widely (21-23). For pattern recognition analysis in clinical study, ANN was also proven to be a promising method (8). 

And the grand concept appeared to be portentous. Quite soon Schramm et al. [2b] aroused enthusiasm with the nonenzymatic synthesis of nucleosides and nucleic acids, and the origin of self-replicating systems the polycondensation of uridylic acid onto the orientating (A) -matrix - and the first attempt at an artificial matrix reaction [2]. Was this the breakthrough that would lead chemistry not only into the wonderland of biology, but also rapidly to ordered and instructed macromolecular organizations in its own dominion [2c-f] ... 

Figure 1. Artificial replicators and matrices (left to right and top to bottom) Rebek s distant nucleoside [6k-m] and v. Kiedrowski s amidinium-carboxylate [7f replicators Lehn s chiral organic [7g] and ele-mentorganic [7h] helicatcs v. Kiedrowski s 6a,b,d-g] and Orgel s [6c] "minimal self-replication systems Hoffmann s alienated nucleic acids [2f, 5c, 7b, lOe] and Luisi s minima-vita approach [5f,g, 8a-d] Eschenmoser s hexosc-nucleic-acids [15], compared with Olson-type R/DNAs and hypothetical nucleation dynamics of nucleoprotein systems [2f, 3k, 5c].

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