Oligonucleotides Containing Modified Bases

The stability of a series of oligonucleotide duplexes containing 7-deaza-7-substituted 2 -deoxyguanosines has been described. The H-phosphonate and phosphoramidite synthons (175a) and (175b) were utilised in S3uithesis and the 

7-iodo substituted oligonucleotide duplexes were found to have enhanced melting temperatures. 

5-Nitroindole and 3-nitropyrrole have been assessed as universal bases in primers for dideoxy sequencing. The 5-nitroindole nucleoside was found to be superior. The melting temperatures of oligonucleotides containing acyclic universal base derivatives (176a) and (176b) was found to exceed those of the 

A fluorescent guanosine analogue has been synthesised and incorporated into oligonucleotides using the synthon (181). The fluorophore within DNA has been used to develop a continuous fluorescence assay for the HFV-l integrase 3 -processing reaction. 

The automated synthesis of platinated oligonucleotides has been achieved using /f-phosphonate oligonucleotide assembly. The platinated thymidine derivative (182) was synthesised from the corresponding /f-phosphonate derivative of thymidine by deprotonation with potassium hydroxide and then reaction with trans-[(NH3)2PtCl2]. 

A new method for the synthesis oligonucleotides containing of 5-formyl-2 -deoxyuridine has been described. The protected phosphoramidite of 5-(l,2-dihydroxyethyl)-2 -deoxyuridine (181) was prepared from 5-iodo-2 -deoxyuridine in seven steps. Following deprotection of the oligomer, subsequent oxidation of the diol with sodium periodate yielded the formyl function which could also be reduced with sodium borohydride to yield the 5-hydroxymethyl compound. An 

The H-phosphonate derivative of a tricyclic carbazole-like 2 -deoxycytidine (183) analogue has been synthesised via a Stille biaryl coupling on 5-iodo-2 -deoxyuridine followed by cyclisation. The carbazole nucleoside was incorporated in oligonucleotides and shown to pair specifically with guanine. Duplexes resulting from the carbazole analogue and complementary RNA have elevated 

The dinucleotide phosphoramidite building block 185 can be utilised to synthesise oligomers containing a pyrimidine(6-4)pyrimidone photoproduct. The unstability of the photoproduct to base necessitated the use of 4-/-(butylphe-noxy)-acetyl protecting groups for dA, dG and dC allowing deprotection of the oligomers in aqueous ammonia at room temperature in two hours. 

Leumann and co-workers have synthesised the nucleoside analogues 7-(2 -deoxy-a-D-ribofuranosyl)hypoxanthine and 7-(2 -deoxy-P-D-ribofuranosyl)hy- 

7-Dimethyl-l-(2-deoxy-P-D-ribofuranosyl)isopterin has been prepared from 6,7-dimethyl-1 -(2-deoxy-3,5-di-0-p-toluoyl-p-D-ribofuranosyl)lumazine via thia-tion and displacement of the thio function with ammonia and then converted into the corresponding N-4-benzoyl and N-4-p-nitrophenylethoxycarbonyl phosphoramidite 192. Mixed oligonucleotides containing 6,7-dimethylisopterin as a modified base have been synthesised using a solid phase phosphoramidite strategy. 

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Compagno, D., Lampe, J.N., Bourget, C., Kutyavin, I.V., Yurchenko, L., Lukhtanov, E.A. and Gom, V.V. (1999) Antisense oligonucleotides containing modified bases inhibit translation of Leishmania amazonensis mRNAs by invading the mini-exon hairpin. J. Biol. Chem., 274, 8191-8198. 

Collision-induced dissociation FAB/MS/MS spectrum of an oligonucleotide containing a modified base. Reproduced (modified) from Iden C.R. and Rieger R.A., Biomed. Environ. Mass Spectrom., 18, 617, 1989, with permission. 

The solid phase synthesis of oligonucleotides containing a site-specific modified psoralen derivative has been accomplished using reagent 197. The base... 

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