BINDING OF OLIGONUCLEOTIDES TO CELL-MEMBRANES AT ACIDIC PH

被引：30

作者：

GOODARZI, G

WATABE, M

WATABE, K

机构：

[1] Department of Medical Microbiology, Immunology Southern Illinois University School of Medicine Springfield

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 1991年 / 181卷 / 03期

基金：

美国国家科学基金会;

关键词：

D O I：

10.1016/0006-291X(91)92086-Y

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：

Antisense oligodeoxynucleotides [oligo(dN)] have the ability to enter living cells and block the expression of specific genes. However, little is known about the mechanism of cellular uptake of oligo(dN). We have found that oligo(dN) can bind to the cell membranes of eukaryotic cells with much greater efficiency under acidic conditions (pH 4.0-4.5) than at neutral pH. The binding appears to be specific to poly nucleic acids since various sizes of oligo(dN), DNA and RNA, but not mononucleotides, compete for the binding. We have identified a 34 kDa membrane protein from T-cells, which binds to oligo(dT) cellulose at pH 4.5 and can be eluted at pH 7.5. This protein fraction blocked the binding of oligo(dN) to living T-cells in a competitive fashion. Our results suggest that eukaryotic cells have a receptor for oligo(dN) at acidic pH and that the 34 kDa dalton protein on the cell membrane may mediate such binding. © 1991.

引用

收藏

页码：1343 / 1351

页数：9

相关论文

共 25 条

[1] CONTROLLED SYNTHESIS OF HBSAG IN A DIFFERENTIATED HUMAN-LIVER CARCINOMA-DERIVED CELL-LINE [J].

ADEN, DP ;

FOGEL, A ;

PLOTKIN, S ;

DAMJANOV, I ;

KNOWLES, BB .

NATURE, 1979, 282 (5739) :615-616

[2] 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

[3] RATE OF DEGRADATION OF [ALPHA]-OLIGODEOXYNUCLEOTIDES AND [BETA]-OLIGODEOXYNUCLEOTIDES IN XENOPUS OOCYTES - IMPLICATIONS FOR ANTI-MESSENGER STRATEGIES [J].

CAZENAVE, C ;

CHEVRIER, M ;

THUONG, NT ;

HELENE, C .

NUCLEIC ACIDS RESEARCH, 1987, 15 (24) :10507-10521

[4]

GAIT MJ, OLIGONUCLEOTIDE SYNT

[5] ANTISENSE OLIGODEOXYRIBONUCLEOTIDES INHIBIT THE EXPRESSION OF THE GENE FOR HEPATITIS-B VIRUS SURFACE-ANTIGEN [J].

GOODARZI, G ;

GROSS, SC ;

TEWARI, A ;

WATABE, K .

JOURNAL OF GENERAL VIROLOGY, 1990, 71 :3021-3025

[6] INHIBITION OF HUMAN IMMUNODEFICIENCY VIRUS-REPLICATION BY ANTISENSE OLIGODEOXYNUCLEOTIDES [J].

GOODCHILD, J ;

AGRAWAL, S ;

CIVEIRA, MP ;

SARIN, PS ;

SUN, D ;

ZAMECNIK, PC .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (15) :5507-5511

[7] HUMAN CUTANEOUS T-CELL LYMPHOMA AND LEUKEMIA-CELL LINES PRODUCE AND RESPOND TO T-CELL GROWTH-FACTOR [J].

GOOTENBERG, JE ;

RUSCETTI, FW ;

MIER, JW ;

GAZDAR, A ;

GALLO, RC .

JOURNAL OF EXPERIMENTAL MEDICINE, 1981, 154 (05) :1403-1418

[8]

KROL AR, 1988, NATURE, V333, P866

[9] SITE SPECIFICITY OF THE INHIBITORY EFFECTS OF OLIGO(NUCLEOSIDE METHYLPHOSPHONATE)S COMPLEMENTARY TO THE ACCEPTOR SPLICE JUNCTION OF HERPES-SIMPLEX VIRUS TYPE-1 IMMEDIATE EARLY MESSENGER RNA-4 [J].

KULKA, M ;

SMITH, CC ;

AURELIAN, L ;

FISHELEVICH, R ;

MEADE, K ;

MILLER, P ;

TSO, POP .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (18) :6868-6872

[10]

LAEMMLI UK, 1970, NATURE, V227, P6807