Conformational studies of 4-N-carbamoyldeoxycytidine derivatives and synthesis and hybridization properties of oligodeoxyribonucleotides incorporating these modified bases

Deoxycytidine derivatives modified with various N-substituted carbamoyl groups at the 4-amino group were synthesized. The detailed H-1 NMR studies suggest that the 3',5'-0disilylated N-carbamoyldeoxycytidine derivative 11 exists as a species having an intramolecular hydrogen bond between the N-3 atom and the carbonyl oxygen atom in MeOD but upon addition of CDCl3, the amount of a homodimer species, having intermolecular hydrogen bonds, gradually increases. Oligodeoxyribonucleotides incorporating various 4-N-carbamoyldeoxycytidine derivatives were also synthesized. These modified oligodeoxynucleotides can hybridize with the complementary strands without disturbing the structure of DNA duplexes, hence changing the orientation of the carbamoyl group in such a manner that a stable Watson-Crick base pair can be formed with the guanine base at the opposite site. It should be noted that the base recognition ability (G against T, C and A) of these modified cytosine bases can be preserved satisfactorily. These results suggest that the 4-N-carbamoyl group is useful as a backbone structure of the linker between various functional residues and oligonucleotides. (c) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006.