Oligonucleotide analogs

Nielsen P.E., Egholm M., Berg R. H., Buchardt O. Peptide nucleic acids (PNA) oligonucleotide analogs with a polyamide backbone. In Antisense Research and Applications. Crooke S.T., Le-BLBu B. (Eds). CRC Press, Boca Raton,... 

Sazani P., Kang S.H., Maier M.A., Wei C., Dillman j., Summerton J., Mano-haran M., Kole R. Nuclear antisense ef fects of neutral, anionic and cationic oligonucleotide analogs. Nucleic Acids Res. 2001 29 3965-3974. 

Recent literature contains many examples of the construction of cascades [56], Usually they are made by the covalent linking of monomer dyes, which allows strict control of their stoichiometry. The pyrene-Bodipy molecular dyads and triads are examples [57]. Efficient energy flow was reported in a purpose-built cascade molecule bearing three distinct chromophores attached to the terminal acceptor [58]. A combinatorial approach with the selection of the best hits can be applied using the assembly of fluorescent oligonucleotide analogs [59]. 

Other known oligonucleotide analogs include oligomers in which the heterocyclic bases have been modified [155] or replaced by other types of compound [156], Solid-phase syntheses of hybrids of DNA with peptides [157-163], with carbohydrates [164,165], and with PNA (peptide nucleic acids, see Section 16.4.1.2 [166-168]) have also been reported, and several strategies have been developed that enable the preparation of oligonucleotides with a modified 5 - or 3 -terminus [169-174] or of cyclic oligonucleotides [122,175], Various techniques for the parallel solid-phase synthesis of oligonucleotides have been developed for the preparation of compound libraries [176-181],... 

H. Sasmor, M. Manoharan, and A.A. Levin. 2001. Pharmacokinetic properties of 2 -0-(2-methoxyethyl)-modified oligonucleotide analogs in rats./. Pharmacol. Exp. Ther. 

T. Schleich, K.L. Tivel, and R.H. Griffey. 1996. Pharmacokinetic properties of several novel oligonucleotide analogs in mice. J. Pharmacol. Exp. Then 277 923-937. 

Synthesis of oligonucleotide analogs with modified side chains 93SL621. 

Henry SP, Zuckerman JE, Rojko J, Hall WC, Harman RJ, Kitchen D, Crooke ST. Toxicological properties of several novel oligonucleotide analogs in mice. Anticancer Drug Des 1997 12 1-14. 

Most antisense experiments made with LNA have been focused mechanistically on mRNA inhibition by RNase H recmitment (7). Expression studies in a wide variety of human epithelial and cancer cell lines are made and the overall picture of these experiments is that LNA antisense oligonucleotides are very potent with IC50 values for mRNA inhibition obtained frequently in the low to sub nanomolar range—and actually more potent than competing oligonucleotide analogs (7). 

Aartsma-Rus A, Kaman WE, Bremmer-Bout M, Janson AA, den Dunnen JT, van Ommen GJ, van Deutekom JC. Comparative analysis of antisense oligonucleotide analogs for targeted DMD 36. exon 46 skipping in muscle cells. Gene Ther. 2004 11 1391-1398. 

Enzymatic hydrolysis of oligonucleotide-analogs containing modified phosphoryl moieties have been examined extensively to study their resistance to the enzymatic hydrolysis. 

Prior to the X-ray analysis, the stereochemical course of the hydrolysis of the Sp diastereomer of thymidine 3 -(4-nitrophenyl [ 0, 0]phosphate) 5 -(4-nitrophenyl phosphate) in H2 0 was determined (26). This synthetic oligonucleotide analog is not a good substrate, and the Sp diastereomer of thymidine 3 -[ 0, 0, 0]phosphate 5 -(4-nitrophenyl phosphate) was obtained as product (recall that on double-stranded DNA the oligonucleotide products contain S -phosphate groups). The simplest explanation for this inversion of configuration is that the enzyme catalyzes the direct attack of water on the phosphodiester backbone of double-stranded DNA, presumably by general basic catalysis. 

Sinha ND, Davis P, Usman N, P6rez J, Hodge R, Kremsky J, Casale R. Labile exocyclic amine protection in DNA, RNA and oligonucleotide analog synthesis facilitating iV-deacylation, minimizing depurination and chain degradation. Biochimie 75 13-23, 1993. 

Iyer RP, Yu D, Ho N-H, Devlin T, Habus Y, Agrawal S. A-Pent-4-enoyl nucleosides Application in the synthesis of support-bound and free oligonucleotide analogs by the /7-phosphonate approach. Tetrahedron Lett 37 1539-1542, 1996. 

Table 5.3 The efflux of oligonucleotide analogs from liposomes...

Akhtar, S., et al. Interactions of antisense DNA oligonucleotide analogs with phospholipid membranes (liposomes). Nucleic Acids Research, 1991, 19(20), 5551-5559. 

Fig. 7 Structural similarity of squaric acid ester and amide and the structures of oligonucleotide analogs containing a squaramide linkage [136,137]...

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