DESIGN OF NEW OLIGONUCLEOTIDE DERIVATIVES RESISTANT TO CELL NUCLEASES DEGRADATION

GOTTIKH, M.; IVANOVSKAYA, M.; SKRIPKIN, E.; SHABAROVA, Z.

Авторы: GOTTIKH MB, IVANOVSKAYA MG, SKRIPKIN EA, SHABAROVA ZA
Журнал: Bioorganicheskaya Khimiya
Том: 16
Номер: 4
Год издания: 1990
Издательство: Izdatel'stva Nauka
Местоположение издательства: Russian Federation
Первая страница: 514
Последняя страница: 523
DOI: ISSN: 0132-3423
Аннотация: Конструирование новых производных олигонуклеотидов, устойчивых к действию клеточных нуклеаз М. Б. Готтих, М. Г. Ивановская, Е. А. Скрипкин, З. А. Шабарова Биоорг. химия 1990, 16 (4):514-523 A new type of modified antisense oligodeoxyribonucleotides is suggested, containing an intercalating drug (e.g., daunomycin (Dnm-NH2)) at one end of the oligonuleotide, and a compound, improving the oligonucleotide transport into the cell, e.g., polymyxin B1 (PmH) at its other end. Schemes for joining these antibiotics to the terminal groups of oligonucleotides have been developed. From undecanucleotide pTGTAAAACGACp (I); the corresponding derivative (Pm)pTGTAAAACGACp (NH-Dnm) (II) was obtained with 20% yield. It was found that joining of daunomycin significantly lowers the rate of the oligonucleotide's exonuclease degradation, whereas joining of polymyxin blocks the degradation completely. Derivative (II) is much more stable to hydrolysis by cell enzymes that the unmodified oligonucleotide (I): upon incubation with E. coli cells (I) is quantitatively hydrolyzed with in 40 minutes while (II) is hydrolyzed by 30% with in 24 h. Derivative (II) is also better adsorbed by E. coli cells. This sort of derivative of antisense oligonucleotides may prove to be efficient inhibitors of the gene expression.
Добавил в систему: Готтих Марина Борисовна

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DESIGN OF NEW OLIGONUCLEOTIDE DERIVATIVES RESISTANT TO CELL NUCLEASES DEGRADATIONстатья

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