Synthesis of site-specific oligonucleotide-polyamine conjugates

Spermine Moiety Attached to the C-5 Position of Deoxyuridine Enhances the Duplex Stability of the Phosphorothioate DNA/Complementary DNA and Shows the Susceptibility of the Substrate to RNase H

“…The magnitude of the stabilization effects was greater than in the case in which the introduction of spermine was carried out at the C-4 position of a deoxycytidine derivative, 10) but was lower than at the C-2 position of the deoxyinosine derivative. 6) This could be attributed to the fact that spermine introduced at the C-2 position of the purine base exists in the minor groove of double helical DNA and forms additional hydrogen bonds between the protonated amine groups and N 3 of purine bases or O-2 of pyrimidine bases, in addition to the possible neutralization of negative charges on the backbone.…”

“…[1][2][3][4][5] One major problem in the use of S-ODNs as antisense molecules is their low thermal stability to the complementary RNAs. In order to overcome this problem, several types of modification such as introduction of a cationic residue, [6][7][8][9][10][11][12][13][14][15] enhancement of the stacking interaction 2,[16][17][18][19][20] and fixation of the sugar conformation [21][22][23][24][25] were explored. Especially, cation-conjugation of oligonucleotide makes amphiphilic molecules to reduce the net negative charge on oligonucleotides, and, therefore, it would bring about improvement of the cell permeability.…”

Non-Nucleosidic Analogues of Polyaminonucleosides and Their Influence on Thermodynamic Properties of Derived Oligonucleotides

“…It was shown previously that polyamine conjugation to oligodeoxyribonucleotides results in stabilizing of DNA duplexes and triplexes [2][3][4]38,39,[41][42][43]. Recently, we described the NMR structure of a DNA duplex carrying a single spermine modified deoxycytidine unit [34].…”

“…The oligomers were cleaved from the CPG-support with 32% aqueous ammonia (room temperature, 1 h). The deprotection under standard conditions using concentrated aqueous ammonia at 55 °C overnight allowed for removal of all protecting groups, including trifluoroacetyls [3,38]. The oligomers were purified by the TLC on Merck 60 F254 TLC plates with n-propanol/aqueous ammonia/water solution (55:35:10, by vol.)…”

“…Many laboratories try to improve nucleic acid delivery to cells by synthesis of cationic bioconjugates [1][2][3], bioconjugate analogues with reduced polyanionic character [4][5][6], or a great variety of polymeric transfection media [7][8][9][10][11][12]. On the other hand, there are studies to elucidate a OPEN ACCESS specific mode of small cationic molecular drugs interactions with biomolecules (e.g., nucleic acids, proteins) useful in developing their more active analogues [13].…”