Factors influencing the extent and selectivity of alkylation within triplexes by reactive G/A motif oligonucleotides

被引:14
作者
Lampe, JN [1 ]
Kutyavin, IV [1 ]
Rhinehart, R [1 ]
Reed, MW [1 ]
Meyer, RB [1 ]
Gamper, HB [1 ]
机构
[1] EPOCH PHARMACEUT INC, BOTHELL, WA 98021 USA
关键词
D O I
10.1093/nar/25.20.4123
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
G/A motif tripler-forming oligonucleotides (TFOs) complementary to a 21 base pair homopurine/homopyrimidine run were conjugated at one or both ends to chlorambucil. These TFOs were incubated with several synthetic duplexes containing the targeted homopurine run flanked by different sequences, The extent of mono and interstrand cross-linking was compared with the level of binding at equilibrium, Covalent modification took place within a triple-stranded complex and usually occurred at guanine residues in the flanking double-stranded DNA, The efficiency of alkylation was dependent upon the sequence of the flanking duplex, the solution conditions, and the rate of tripler formation relative to the rate of chlorambucil reaction, Self-association of the TFOs as parallel duplexes was demonstrated and this did not interfere with triple strand formation, With an optimal target, cross-linking of the tripler was very efficient when incubation was carried in a physiological buffer supplemented with the tripler selective intercalator coralyne.
引用
收藏
页码:4123 / 4131
页数:9
相关论文
共 35 条
[1]   DNA sequence specificity of a naphthylquinoline triple helix-binding ligand [J].
Cassidy, SA ;
Strekowski, L ;
Fox, KR .
NUCLEIC ACIDS RESEARCH, 1996, 24 (21) :4133-4138
[2]   KINETICS OF CHLORAMBUCIL HYDROLYSIS USING HIGH-PRESSURE LIQUID-CHROMATOGRAPHY [J].
CHATTERJI, DC ;
YEAGER, RL ;
GALLELLI, JF .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1982, 71 (01) :50-54
[3]   MONOVALENT CATION EFFECTS ON INTERMOLECULAR PURINE-PURINE-PYRIMIDINE TRIPLE-HELIX FORMATION [J].
CHENG, AJ ;
VANDYKE, MW .
NUCLEIC ACIDS RESEARCH, 1993, 21 (24) :5630-5635
[4]   STABILITIES OF DOUBLE-STRAND AND TRIPLE-STRAND HELICAL NUCLEIC-ACIDS [J].
CHENG, YK ;
PETTITT, BM .
PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY, 1992, 58 (03) :225-257
[5]   Interstrand cross-linking reaction in triplexes containing a monofunctional transplatin-adduct [J].
Colombier, C ;
Lippert, B ;
Leng, M .
NUCLEIC ACIDS RESEARCH, 1996, 24 (22) :4519-4524
[6]   SITE-SPECIFIC OLIGONUCLEOTIDE BINDING REPRESSES TRANSCRIPTION OF THE HUMAN C-MYC GENE INVITRO [J].
COONEY, M ;
CZERNUSZEWICZ, G ;
POSTEL, EH ;
FLINT, SJ ;
HOGAN, ME .
SCIENCE, 1988, 241 (4864) :456-459
[7]   SPECIFIC-INHIBITION OF TRANSCRIPTION BY TRIPLE HELIX-FORMING OLIGONUCLEOTIDES [J].
DUVALVALENTIN, G ;
THUONG, NT ;
HELENE, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (02) :504-508
[8]   TRIPLEX FORMATION INHIBITS HER-2 NEU TRANSCRIPTION IN-VITRO [J].
EBBINGHAUS, SW ;
GEE, JE ;
RODU, B ;
MAYFIELD, CA ;
SANDERS, G ;
MILLER, DM .
JOURNAL OF CLINICAL INVESTIGATION, 1993, 92 (05) :2433-2439
[9]   Ligand-induced formation of triple helices with antiparallel third strands containing G and T [J].
Escude, C ;
Sun, JS ;
Nguyen, CH ;
Bisagni, E ;
Garestier, T ;
Helene, C .
BIOCHEMISTRY, 1996, 35 (18) :5735-5740
[10]   Stable triple helices formed by oligonucleotide N3'->P5' phosphoramidates inhibit transcription elongation [J].
Escude, C ;
Giovannangeli, C ;
Sun, JS ;
Lloyd, DH ;
Chen, JK ;
Gryaznov, SM ;
Garestier, T ;
Helene, C .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (09) :4365-4369