Conformational Studies of 4‐N‐Carbamoyldeoxycytidine Derivatives and Synthesis and Hybridization Properties of Oligodeoxyribonucleotides Incorporating these Modified Bases

Abstract

Deoxycytidine derivatives modified with various N‐substituted carbamoyl groups at the 4‐amino group were synthesized. The detailed 1H NMR studies suggest that the 3′,5′‐O‐disilylated N‐carbamoyldeoxycytidine derivative 11 exists as a species having an intramolecular hydrogen bond between the N3 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. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Oligonucleotide Analogues with Integrated Bases and Backbone. Part 27

“…This assignment is corroborated by the HMBC spectrum of the p-toluenesulfonate derived from 2 (data not given), especially by cross-peaks between the again rather sharp signal of C(4) at 162 ppm and both the HÀC(5) and HÀC(6) signals. We differ from the opinion of Sekine and coworkers [21] by assuming that tautomer T3 (weaker C(5)ÀH ··· O¼C H-bond than in T1) does not contribute significantly to the tautomeric equilibrium. The relatively weak downfield shift of PhC¼O (166 ppm) suggests an equilibrium between T1 and only one imino tautomer.…”

N 4-acyl-2′-deoxycytidine-5′-triphosphates for the enzymatic synthesis of modified DNA

“…Nevertheless, it is more complicated than an unusual mismatched base-pairing. For instance, it has been determined that N 4 -acyl groups are oriented in a geometrically fixed manner that makes the formation of conventional Watson–Crick type base pairs with the guanine residue, owing to an intramolecular hydrogen bond between the carbonyl oxygen atom and the 5-vinyl proton of the cytosine ring ( 64 ). In contrast, N 4 -carbamoyl-dC•G base-pairing occurs only in a form of ONs, suggesting that geometry of N 4 -substituents strongly depends on the salvation and intramolecular hydrogen bonds ( 64 ).…”

“…For instance, it has been determined that N 4 -acyl groups are oriented in a geometrically fixed manner that makes the formation of conventional Watson–Crick type base pairs with the guanine residue, owing to an intramolecular hydrogen bond between the carbonyl oxygen atom and the 5-vinyl proton of the cytosine ring ( 64 ). In contrast, N 4 -carbamoyl-dC•G base-pairing occurs only in a form of ONs, suggesting that geometry of N 4 -substituents strongly depends on the salvation and intramolecular hydrogen bonds ( 64 ). Although there are several reports on the decreased stability of DNA duplexes upon increasing alkyl chain length in the N 4 -acyl group of cytidine ( 45 ), we have failed to notice such tendency during the PEX experiments.…”

New thermolytic carbamoyl groups for the protection of nucleobases

“…The carbamoylated dC and dA derivatives (2a-c, f, h, i) have the corresponding conformers containing an intramolecular hydrogen bond via a 6-membered ring between the carbamoyl group and the ring nitrogen atom of the nucleobase, 11 as shown in Fig. 1-A and -B.…”