Oligonucleotides containing 5-fluoro-2'-deoxyCytidine are effective inhibitors of DNA methyltransferases. Two serious problems have impeded efforts to produce oligonucleotides containing F-dC. The presence of the fluorine residue makes acyl protection of the amino group very difficult. Also, the deoxynucleoside itself is very expensive. Both of these problems are circumvented by the use of a Convertible Nucleoside strategy1: 4-O-(2,4,6-trimethylphenyl)-5-fluoro-2'-deoxyUridine (TMP-F-dU) is converted into F-dC after oligonucleotide synthesis by the ammonium hydroxide used for the routine deprotection steps.
Also available for the first time are 2-aminopurine and 8-bromo-dG monomers. The former may be used for structural studies and the latter for cross-linking. We hope to add 8-oxo-dG, 8-bromo-dA, 8-oxo-dA, and convertible dI monomers soon.
(1) A.M. MacMillan, L. Chen, and G.L. Verdine, J. Org. Chem., 1992, 57, 2989-2991.