A-oligodeoxynucleotides

Fig. 10.6 S imulation of tissue oligonucleotide concentrations for a daily oral dosing regimen of one-month duration for a oligodeoxynucleotide (A) or a MOE gapmer chemistry (B) at 2 mg/kg using a variable bioavailability input metric randomly generated from 2 to 15% (geometric mean 7%).

Figure 1.59 Full structural illustration of a oligodeoxynucleotide (left) and various shorthand structures (right) commonly used to define oligo-polydeoxynucleotide structures simply. Similar short hand structures exist for oligo-polynucleotide structures except that "d" for "deoxy" is dispensed with.

Steps Involved in One Elongation Cycle for the Synthesis of a-Oligodeoxynucleotides... 

In order to synthesize a-oligodeoxynucleotides, we first needed the a-deoxynucleosides corresponding to the four natural bases in sufficient amount (multigram scale) since they are not—except a-dT—commercially available. Thus, we scaled up procedures already described or developed new ones, and selected those that gave the best results with respect to efficiency. 

Last, the synthesis of a-oligodeoxynucleotides requires the same reagents and the same elongation cycles as for P-oligodeoxy-nucleotide synthesis. Likewise, a-oligodeoxynucleotides are deprotected and purified by following the standard procedures. 

In conclusion, the synthesis of a-oligodeoxynucleotides containing the four natural bases is as easy as that of P-oligodeoxynucleotides. Furthermore, a-oligodeoxynucleoside phosphorothioates can be obtained with ease by substitution of the oxidation step with the sulfur-ization step either with elemental sulfur (J6)ot H- 1,2-benzodithiole-3-one 1,1-dioxyde (17)hy following the standard conditions. 

Fig. 11. The amidite method for synthesizing oligodeoxynucleotides, where B and represent one of the protected bases thymine, A/ -benzoylcytosine,...

Probe A molecule used to detect the presence of a specific fragment of DNA or RNA in, for instance, a bacterial colony that is formed from a genetic library or during analysis by blot transfer techniques common probes are cDNA molecules, synthetic oligodeoxynucleotides of defined sequence, or antibodies to specific proteins. 

Single-stranded oligodeoxynucleotides were even more effective than dA at preserving the reactivity of QMP11 in an aqueous solution. A mere 3 pM of 5 -d... 

Stein, C. A. and Cohen, J. S., Phosphorothioate oligodeoxynucleotide analogues, in Oligodeoxynucleotides — Antisense Inhibitors of Gene Expression, Cohen, J. S., Ed., CRC Press, Boca Raton, FL, 1989, 97. 

Finally a few sentences are deserved for the vast area of DNA photochemistry. Thymine dimerization is the most common photochemical reaction with the quantum yield of formation in isolated DNA of all-thymine oligodeoxynucleotides 2-3% [3], Furthermore, a recent study based on femtosecond time-resolved transient absorption spectroscopy showed that thymine dimers are formed in less than 1 ps when the strand has an appropriate conformation [258], The low quantum yield of the reaction in regular DNA is suggested to be due to the infrequency of these appropriate reactive conformations. 

Okamoto A, Ichiba T, Saito I (2004) Pyrene-labeled oligodeoxynucleotide probe for detecting base insertion by excimer fluorescence emission. J Am Chem Soc 126 8364—8365... 

In protozoa this problem is solved by the addition of preexisting oligodeoxynucleotide blocks to the 3 ends of DNA. These blocks are composed of tandemly repeated units of (T2G4)n or (T4G4)n, where n is approximately 50. The enzyme that adds these polymers requires a primer but not a template. These oligonucleotide block polymers are called telomers. Another DNA polymerase,... 

Standifer K, Chien C, Wahlstedt C, Brown G, Pasternak G. Selective loss of delta opioid analgesia and binding by antisense oligodeoxynucleotide to a delta opioid receptor. Neuron 1994 12 805-810. 

Gaur, R., Sharma, S., and Gupta, K.C. (1989) A simple method for the introduction of thiol group at 5 -termini of oligodeoxynucleotides. Nucleic Acids Res. 17, 4404. 

Kiyama, H., Emson, P.C., and Tokyama, M. (1992) In situ hybridization histochemistry using alkaline phosphatase-labeled oligodeoxynucleotide probe. In Methods in Molecular Biology, Protocols in Molecular Neurobiology, (A. Longstaff, and R Revest, eds.), Vol. 13, pp. 167-179. Humana Press, Totowa, New Jersey. 

Alvarez-Salas, L.M., Benitez-Hess, M.L., and DiPaolo, J.A. 2003. Advances in the development of ribozymes and antisense oligodeoxynucleotides as antiviral agents for human papillomaviruses. Antiviral Therapy 8(4), 265-278. 

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