Oligonucleotide pyrimidine base

The propeller twist bases in base pairs are rarely co-planar. When unsubstituted pyrimidine and purine bases crystallize in the form of homo or hetero base pairs (Part II, Chap. 16), these are generally planar due to symmetry requirements. If such symmetry constraints are absent, as in co-crystal of nucleosides or nucleotides or in crystals of oligonucleotides, the bases in the pairs are usually twisted... 

Nucleic acids in which various purine and pyrimidine bases are united by bridges of D-2-deoxyribose or D-2-ribose phosphoric acid play vital roles in the metabolism of living cells.179 Many oligonucleotides (which are heterocyclic co-oligomers) have been synthesized in studying the biochemistry of nucleic acids.180... 

Monaharan has developed a versatile synthetic route for the synthesis of 2 -0-[(N, iV-dimethylamino)-oxyethyl] modified purine and pyrimidine nucleoside phosphoramidites (63a-d) to be used as antisense oligonucleotide building blocks. In the syntheses of the purine-based analogues, the (iV, N-dimethylamino)-oxyethyl group was introduced via a 2 -allyloxy nucleoside intermediate, while the pyrimidine-based nucleosides were obtained from the TBDMS-protected 2,2 -anhydro-5-methyluridine via ring opening reaction in the presence of borane and ethylene glycol. The aminoxy derivatives were... 

Nucleases, such as ribonuclease (RNase) A or T, catalyze the hydrolysis of phospho-diester bonds in nucleic acids to produce oligonucleotides. Whereas the mammalian-type nuclease RNase A requires a pyrimidine base on the (3 )-side of the substrate, the microbial enzyme RNase T, requires a guanine [116]. Although the two families show hardly any sequence homology or structural relation, the cleavage mechanisms are believed to be similar [117-119]. 

Modeling Duplex DNA Oligonucleotides with Modified Pyrimidine Bases... 

Hydrolysis of nucleic acids may lead to oligonucleotides, mononucleotides, nucleosides, purine and pyrimidine bases, sugar phosphates and free carbohydrates. Secondary products always result also, e. g., from deamination of the aminopurines and aminop3uimidines or their nucleosides and nucleotides. 

The identification of DNA as a primary target for metal-based drugs, especially cisplatin, has focused attention on the interactions of metal complexes with nucleic acid constituents, which include the simple purine and pyrimidine bases and their nucleoside and nucleotide derivatives. The structures, with abbreviations, are represented in Appendix 1. Simple complexes can represent models for cross links in DNA, which can be studied in more detail with small polynucleotides, from the simpler dinucleotides to oligonucleotides and this topic is covered in Section 4.4. There has been extensive use of substituted purines and pyrimidines as models for the DNA bases and in the examination of steric and electronic effects. The structures of many of these analogues are also collected in Appendix 1. 

The ability of o-QM to form several metastable adducts with pyrimidine (at cytosine N3) and purine bases (at guanine N7 and adenine Nl) in water suggested that the above adducts may be exploited as o-QM carriers under mild conditions, anticipating that o-QM could actually migrate along the structure of an oligonucleotide.35... 

Nucleotides can be linked together into oligonucleotides through a phosphate bridge at the 5 position of one ribose unit and the 3 position of another. The purine bases, adenine and guanine, have two heterocyclic rings, while the pyrimidines cytosine, thymine, and uracil have one. The structure of adenosine monophosphate is shown in Figure 11. 

Figure 27.1 Three common nucleoside triphosphate derivatives that can be incorporated into oligonucleotides by enzymatic means. The first two are biotin derivatives of pyrimidine and purine bases, respectively, that can be added to an existing DNA strand using either polymerase or terminal transferase enzymes. Modification of DNA with these nucleosides results in a probe detectable with labeled avidin or streptavidin conjugates. The third nucleoside triphosphate derivative contains an amine group that can be added to DNA using terminal transferase. The modified oligonucleotide then can be labeled with amine-reactive bioconjugation reagents to create a detectable probe.

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