Deoxyribose analoges

Anion Electron-Stimulated Desorption from Thin Films of Deoxyribose Analogs... 

The synthetic protocols used for the preparation of oligonucleotides on supports can also be used to prepare oligomers from diols other than nucleosides. Symmetric or unsymmetric diols, such as N-acylated 4-hydroxyprolinol [268] or cyclopentane-derived diols (carbocyclic deoxyribose analogs [269]), can be selectively mono-trity-lated and then converted into a phosphoramidite that is suitable for the solid-phase synthesis of oligophosphates. An illustrative synthesis of protected //-phosphonates from diols, as well as their conversion on CPG into oligomeric phosphoramidates, are outlined in Figure 16.28. 

Figure 19-6. The H yield function from thin films of (A) double stranded linear DNA, 40 base-pairs, (B) supercoiled plasmid DNA, (C) thymine, (D) ice, and (E) a deoxyribose analog. The zero-count baseline of curves A-D has been displaced for clarity. Part of a single DNA strand is shown in the left corner at the top. The dependence of the magnitude of the II signal from DNA on time of exposure to the electron beam is shown in the insert...

The transformation of ribonucleotides to their deoxyribose analogs by particulate free extracts of E. coK B has been described. The actual conversion appears to take place at the diphosphate level, i.e., cytidine diphosphate (GDP) conversion to deoi -CDP. TPNH is required for this enzymic reductive reaction. ATP and Mg stimulate deoxynucleotide formation although their precise role is unknown 93). 

An analogous series of reactions is used to produce depyrimidinated DNA fragments. Hydrazine is used in these reactions, since both cytosine and thymine react with hydrazine. The bases are cleaved to yield urea and a pyrazole ring. The deoxyribose moiety is left as a hydrazone. Piperidine, which reacts with the hydrazone, is used to cleave the nucleotide chain. Cytosines react specifically with hydrazine in 5 mol/ L NaCl, but no specific reaction exists for thymines. Consequently, one aliquot yields labeled oligonu-cleotides 3 -terminated at cytosines, whereas a second aliquot contains nucleotides cleaved in the absence of NaCI at both cytosine and thymine residues. 

Other 1,3-diazaheterocycles related to the benzimidazole system that can be lithiated include purine nucleosides 53-55 and the related cordy-cepin analogs 56, which undergo lithiation with LDA at the 8-position when the ribose or deoxyribose hydroxy groups, are suitably protected (87CPB72 89JHCI89). Some aspects of the nucleoside metalation work have been recently reviewed (89MII). 

Where nucleic acids are concerned, the enhanced hydrophobicity of abiotic polyfluorinated aromatic bases (e.g., tetrafluorobenzene or tetrafluoroindole deoxyribose derivatives) was exploited as an alternative to natural hydrogen bonding to achieve selective and stable nucleic acid base pairing in duplex DNA [85], The DNA replication was examined using polyfluorinated-nucleotide analogs as substrates. A DNA polymerase active site was able to process the polyfluorinated base pairs more effectively than the analogous hydrocarbon pairs, demonstrating hydrophobic selectivity of polyfluorinated bases for other polyfluorinated bases [86]. 

DNA chain growth can be blocked by the incorporation of certain nucleoside analogs that have been modified in the sugar portion of the nucleoside (Figure 29.24).7 For example, removal of the hydroxyl group from the 3 -carbon of the deoxyribose ring as in 2, 3 -dldeoxyiriosirie (ddl), or conversion of the deoxyribose to another... 

Cytosine arabinoside (Cytarabine, Cytosar, and Ara-C) is an analog of deoxycytidine, differing only in its substitution of sugar arabinose for deoxyribose. It is converted to Ara-CTP, and thereby inhibits DNA polymerase according to the following reactions ... 

Figure 22.4. Structural comparison between a natural AP site and its analog THF (tetrahy-drofuran). The deoxyribose at the natural AP site exists in equilibrium between an open-chain aldehyde and a closed-chain furanose.

Fig. 15.1. The four bases found in the nucleic acids. Uracil occurs in RNA and is substituted by the analogous thymine (5-methyluracil) in DNA. Uracil is the keto tautomer of 2,4-dihydroxy pyrimidine with two donors N(1)H, N(3)H and two acceptors 0(2), 0(4). Cytosine is the keto tautomer of 4-amino, 2-hydroxy pyrimidine with three donors N(4)H2, N(1)H and two acceptors 0(2), N(3). Adenine is 6-aminopurine with three donors N(6)H2, N(9)H and three acceptors N(l), N(3), N(7). Guanine is the keto tautomer of 2-amino, 6-hydroxy purine with three donors N(2)H2, N(9)H and three acceptors, N(3), N(7), 0(6). In the nucleosides, pyrimidine N(l) and purine N(9) are substituted by ribose or deoxyribose (see Fig. 17.1)...

The reactions of these radicals in aqueous solution are particularly interesting, because of their model character with respect to deoxyribose-derived radicals in DNA [83], which lead to strand breaks of this macromolecule. These model reactions have been studied in detail [84], by use of a large number of substrates, with the help of in-situ photolysis ESR, time-resolved conductance, and product-analysis techniques. From the results it is evident that the primarily formed a-alkoxy-jff-chlor-oalkyl radicals in aqueous solution undergo heterolysis of the jff-C-Cl bond with rates A het > 10 s to give rise, finally, to the y -OH-substituted analogs which were identified by ESR. 

The analogous D-ribonucleotides of the other purines and pyrimidines are uridylic acid, guanylic acid, and cytidylic acid. Thymidylic acid is the 5 -monophosphate of thymidine (the carbohydrate is 2-deoxyribose in this case). 

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