Effects of γ-turn and β-tail amino acids on sequence-specific recognition of DNA by hairpin polyamides

被引:68
作者
Swalley, SE [1 ]
Baird, EE [1 ]
Dervan, PB [1 ]
机构
[1] CALTECH, Div Chem & Chem Engn, Pasadena, CA 91125 USA
关键词
D O I
10.1021/ja9830905
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Three-ring polyamides containing pyrrole (Py) and imidazole (Im) amino acids covalently coupled by a turn-specific gamma-aminobutyric acid linker (gamma-turn) form six-ring hairpins that recognize predetermined 5-base pair (bp) sequences in the minor groove of DNA. To determine the sequence specificity of the gamma-turn and C-terminal beta-alanine (beta-tail) amino acids, the DNA-binding properties of the hairpin polyamide ImImPy-gamma-ImPyPy-beta-Dp were analyzed by footprinting and affinity cleavage on DNA-restriction fragments containing the eight possible 5'-ATGGCNA-3' and 5'-ANGGCTA-3' sites (N = A, T,G or C; 5-bp hairpin site is in italics). Quantitative footprint titrations demonstrate that both the gamma-turn and beta-tail amino acids have a > 200-400-fold preference for A.T/T.A relative to G.C base pairs at these positions, Effects of the base pairs adjacent to the 5-bp hairpin-binding site were analyzed by footprinting experiments on a DNA-restriction fragment containing the eight possible 5'-ATGGCTN-3' and 5'-NTGGCTA-3' sites, Quantitative footprint titrations demonstrate that the turn and tail amino acids have reduced specificity (3-20-fold preference) for A.T/T.A relative to G.C base pairs at these positions. These results indicate that the turn and tail amino acids do not simply act as neutral linker residues but, in fact, are sequence-specific recognition elements with predictable DNA-binding specificity.
引用
收藏
页码:1113 / 1120
页数:8
相关论文
共 61 条
[1]  
[Anonymous], 1989, SYNTHETIC OLIGONUCLE
[2]   Solid phase synthesis of polyamides containing imidazole and pyrrole amino acids [J].
Baird, EE ;
Dervan, PB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1996, 118 (26) :6141-6146
[3]   FOOTPRINT TITRATIONS YIELD VALID THERMODYNAMIC ISOTHERMS [J].
BRENOWITZ, M ;
SENEAR, DF ;
SHEA, MA ;
ACKERS, GK .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1986, 83 (22) :8462-8466
[4]  
BRENOWITZ M, 1986, METHOD ENZYMOL, V130, P132
[5]   BINDING OF 2 DISTAMYCIN-A MOLECULES IN THE MINOR-GROOVE OF AN ALTERNATING B-DNA DUPLEX [J].
CHEN, X ;
RAMAKRISHNAN, B ;
RAO, ST ;
SUNDARALINGAM, M .
NATURE STRUCTURAL BIOLOGY, 1994, 1 (03) :169-175
[6]   A NEW DNA MINOR-GROOVE BINDING MOTIF - CROSS-LINKED LEXITROPSINS [J].
CHEN, YH ;
LOWN, JW .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1994, 116 (16) :6995-7005
[7]   A BIFURCATED HYDROGEN-BONDED CONFORMATION IN THE D(A.T) BASE-PAIRS OF THE DNA DODECAMER D(CGCAAATTTGCG) AND ITS COMPLEX WITH DISTAMYCIN [J].
COLL, M ;
FREDERICK, CA ;
WANG, AHJ ;
RICH, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (23) :8385-8389
[8]   NMR characterization of hairpin polyamide complexes with the minor groove of DNA [J].
deClairac, RPL ;
Geierstanger, BH ;
Mrksich, M ;
Dervan, PB ;
Wemmer, DE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (34) :7909-7916
[9]   Inhibition of RNA polymerase II transcription in human cells by synthetic DNA-binding ligands [J].
Dickinson, LA ;
Gulizia, RJ ;
Trauger, JW ;
Baird, EE ;
Mosier, DE ;
Gottesfeld, JM ;
Dervan, PB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :12890-12895
[10]   STRUCTURAL-ANALYSIS OF COVALENT PEPTIDE DIMERS, BIS(PYRIDINE-2-CARBOXAMIDONETROPSIN)(CH2)3-6, IN COMPLEX WITH 5'-TGACT-3' SITES BY 2-DIMENSIONAL NMR [J].
DWYER, TJ ;
GEIERSTANGER, BH ;
MRKSICH, M ;
DERVAN, PB ;
WEMMER, DE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (22) :9900-9906