Kinetic analysis of specificity of duplex DNA targeting by homopyrimidine peptide nucleic acids

被引:31
作者
Demidov, VV [1 ]
Yavnilovich, MV [1 ]
FrankKamenetskii, MD [1 ]
机构
[1] WEIZMANN INST SCI,DEPT BIOL STRUCT,IL-76100 REHOVOT,ISRAEL
关键词
D O I
10.1016/S0006-3495(97)78918-5
中图分类号
Q6 [生物物理学];
学科分类号
071011 ;
摘要
A simple theoretical analysis shows that specificity of double-stranded DNA (dsDNA) targeting by homopyrimidine peptide nucleic acids (hpyPNAs) is a kinetically controlled phenomenon. Our computations give the optimum conditions for sequence-specific targeting of dsDNA by hpyPNAs. The analysis shows that, in agreement with the available experimental data, kinetic factors play a crucial role in the selective targeting of dsDNA by hpyPNAs. The selectivity may be completely lost if PNA concentration is too high and/or during prolonged incubation of dsDNA with PNA. However, quantitative estimations show that the experimentally observed differences in the kinetic constants for hpyPNA binding with the correct and mismatched DNA sites are sufficient for sequence-specific targeting of long genomic DNA by hpyPNAs with a high yield under appropriate experimental conditions. Differential dissociation of hpyPNA/dsDNA complexes is shown to enhance the selectivity of DNA targeting by PNA.
引用
收藏
页码:2763 / 2769
页数:7
相关论文
共 31 条
[1]  
[Anonymous], 1993, ANTISENSE RES APPL
[2]   Enhanced peptide nucleic acid binding to supercoiled DNA: Possible implications for DNA ''breathing'' dynamics [J].
Bentin, T ;
Nielsen, PE .
BIOCHEMISTRY, 1996, 35 (27) :8863-8869
[3]   A NUCLEIC-ACID TRIPLE-HELIX FORMED BY A PEPTIDE NUCLEIC-ACID DNA COMPLEX [J].
BETTS, L ;
JOSEY, JA ;
VEAL, JM ;
JORDAN, SR .
SCIENCE, 1995, 270 (5243) :1838-1841
[4]   DNA UNWINDING UPON STRAND-DISPLACEMENT BINDING OF A THYMINE-SUBSTITUTED POLYAMIDE TO DOUBLE-STRANDED DNA [J].
CHERNY, DY ;
BELOTSERKOVSKII, BP ;
FRANKKAMENETSKII, MD ;
EGHOLM, M ;
BUCHARDT, O ;
BERG, RH ;
NIELSEN, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (05) :1667-1670
[5]   BACKBONE MODIFICATIONS IN OLIGONUCLEOTIDES AND PEPTIDE NUCLEIC-ACID SYSTEMS [J].
DEMESMAEKER, A ;
ALTMANN, KH ;
WALDNER, A ;
WENDEBORN, S .
CURRENT OPINION IN STRUCTURAL BIOLOGY, 1995, 5 (03) :343-355
[6]   SEQUENCE SELECTIVE DOUBLE-STRAND DNA CLEAVAGE BY PEPTIDE NUCLEIC-ACID (PNA) TARGETING USING NUCLEASE S1 [J].
DEMIDOV, V ;
FRANKKAMENETSKII, MD ;
EGHOLM, M ;
BUCHARDT, O ;
NIELSEN, PE .
NUCLEIC ACIDS RESEARCH, 1993, 21 (09) :2103-2107
[7]   KINETICS AND MECHANISM OF POLYAMIDE (PEPTIDE) NUCLEIC-ACID BINDING TO DUPLEX DNA [J].
DEMIDOV, VV ;
YAVNILOVICH, MV ;
BELOTSERKOVSKII, BP ;
FRANKKAMENETSKII, MD ;
NIELSEN, PE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (07) :2637-2641
[8]   ELECTRON-MICROSCOPY MAPPING OF OLIGOPURINE TRACTS IN DUPLEX DNA BY PEPTIDE NUCLEIC-ACID TARGETING [J].
DEMIDOV, VV ;
CHERNY, DI ;
KURAKIN, AV ;
YAVNILOVICH, MV ;
MALKOV, VA ;
FRANKKAMENETSKII, MD ;
SONNICHSEN, SH ;
NIELSEN, PE .
NUCLEIC ACIDS RESEARCH, 1994, 22 (24) :5218-5222
[9]   STABILITY OF PEPTIDE NUCLEIC-ACIDS IN HUMAN SERUM AND CELLULAR-EXTRACTS [J].
DEMIDOV, VV ;
POTAMAN, VN ;
FRANKKAMENETSKII, MD ;
EGHOLM, M ;
BUCHARD, O ;
SONNICHSEN, SH ;
NIELSEN, PE .
BIOCHEMICAL PHARMACOLOGY, 1994, 48 (06) :1310-1313
[10]  
DEMIDOV VV, 1996, BIOL STRUCTURE DYNAM, V2, P129