SELF-STABILIZED ANTISENSE OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES - PROPERTIES AND ANTI-HIV ACTIVITY

被引:100
作者
TANG, JY [1 ]
TEMSAMANI, J [1 ]
AGRAWAL, S [1 ]
机构
[1] HYBRIDON INC, 1 INNOVAT DR, WORCESTER, MA 01605 USA
关键词
D O I
10.1093/nar/21.11.2729
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
A new class of oligodeoxyribonucleotides has been designed, referred to here as 'self-stabilized' oligonucleotides. These oligonucleotides have hairpin loop structures at their 3' ends, and show increased resistance to degradation by snake venom phosphodiesterase, DNA polymerase I and fetal bovine serum. The self-stabilized region of the oligonucleotide does not interfere In hybridization with complementary nucleic acids as shown by melting temperature, mobility-shift and RNase H cleavage studies. Various self-stabilized oligonucleotides containing increasingly stable hairpin loop regions were studied for their anti-HIV activity. Pharmacokinetic and stability studies in mice showed increased in vivo persistence of self-stabilized oligonucleotides with respect to their linear counterparts.
引用
收藏
页码:2729 / 2735
页数:7
相关论文
共 29 条
[1]   PHARMACOKINETICS, BIODISTRIBUTION, AND STABILITY OF OLIGODEOXYNUCLEOTIDE PHOSPHOROTHIOATES IN MICE [J].
AGRAWAL, S ;
TEMSAMANI, J ;
TANG, JY .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1991, 88 (17) :7595-7599
[2]  
Agrawal S, 1992, Antisense Res Dev, V2, P261
[3]   EFFICIENT SYNTHESIS OF OLIGORIBONUCLEOTIDE AND ITS PHOSPHOROTHIOATE ANALOG USING H-PHOSPHONATE APPROACH [J].
AGRAWAL, S ;
TANG, JY .
TETRAHEDRON LETTERS, 1990, 31 (52) :7541-7544
[4]   INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS IN EARLY INFECTED AND CHRONICALLY INFECTED-CELLS BY ANTISENSE OLIGODEOXYNUCLEOTIDES AND THEIR PHOSPHOROTHIOATE ANALOGS [J].
AGRAWAL, S ;
IKEUCHI, T ;
SUN, D ;
SARIN, PS ;
KONOPKA, A ;
MAIZEL, J ;
ZAMECNIK, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (20) :7790-7794
[5]   ANTISENSE OLIGONUCLEOTIDES AS ANTIVIRAL AGENTS [J].
AGRAWAL, S .
TRENDS IN BIOTECHNOLOGY, 1992, 10 (05) :152-158
[6]   OLIGODEOXYNUCLEOSIDE PHOSPHORAMIDATES AND PHOSPHOROTHIOATES AS INHIBITORS OF HUMAN IMMUNODEFICIENCY VIRUS [J].
AGRAWAL, S ;
GOODCHILD, J ;
CIVEIRA, MP ;
THORNTON, AH ;
SARIN, PS ;
ZAMECNIK, PC .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (19) :7079-7083
[7]   OLIGODEOXYNUCLEOSIDE METHYLPHOSPHONATES - SYNTHESIS AND ENZYMATIC DEGRADATION [J].
AGRAWAL, S ;
GOODCHILD, J .
TETRAHEDRON LETTERS, 1987, 28 (31) :3539-3542
[8]   ANTISENSE OLIGONUCLEOTIDES - GENE-REGULATION AND CHEMOTHERAPY OF AIDS [J].
AGRAWAL, S ;
SARIN, PS .
ADVANCED DRUG DELIVERY REVIEWS, 1991, 6 (03) :251-270
[9]  
AGRAWAL S, 1992, GENE REGULATION BIOL, P273
[10]  
AGRAWAL S, 1992, ANTISENSE RNA DNA, P305