Binding site size limit of the 2:1 pyrrole-imidazole polyamide-DNA motif

被引:93
作者
Kelly, JJ [1 ]
Baird, EE [1 ]
Dervan, PB [1 ]
机构
[1] CALTECH,DIV CHEM & CHEM ENGN,PASADENA,CA 91125
关键词
D O I
10.1073/pnas.93.14.6981
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids can be combined in antiparallel side-by-side dimeric complexes for sequence-specific recognition in the minor groove of DNA. Six polyamides containing three to eight rings bind DNA sites 5-10 bp in length, respectively. Quantitative DNase I footprint titration experiments demonstrate that affinity maximizes and is similar at ring sizes of five, six, and seven. Sequence specificity decreases as the length of the polyamides increases beyond five rings. These results provide useful guidelines for the design of new polyamides that bind longer DNA sites with enhanced affinity and specificity.
引用
收藏
页码:6981 / 6985
页数:5
相关论文
共 20 条
[1]   DESIGN, SYNTHESIS, DNA-BINDING, AND BIOLOGICAL-ACTIVITY OF A SERIES OF DNA MINOR-GROOVE-BINDING INTERCALATING DRUGS [J].
BAILLY, C ;
POMMERY, N ;
HOUSSIN, R ;
HENICHART, JP .
JOURNAL OF PHARMACEUTICAL SCIENCES, 1989, 78 (11) :910-917
[2]   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
[3]  
CHEN X, 1994, STRUCT BIOL, V1, P169
[4]   NMR CHARACTERIZATION OF A HETEROCOMPLEX FORMED BY DISTAMYCIN AND ITS ANALOG 2-IMD WITH D(CGCAAGTTGGC)-D(GCCAACTTGCG) - PREFERENCE FOR THE 1/1/1 2-IMD-DST-DNA COMPLEX OVER THE 2/1 2-IMD-DNA AND THE 2/1 DST-DNA COMPLEXES [J].
GEIERSTANGER, BH ;
DWYER, TJ ;
BATHINI, Y ;
LOWN, JW ;
WEMMER, DE .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (11) :4474-4482
[5]   STRUCTURAL AND DYNAMIC CHARACTERIZATION OF THE HETERODIMERIC AND HOMODIMERIC COMPLEXES OF DISTAMYCIN AND 1-METHYLIMIDAZOLE-2-CARBOXAMIDE-NETROPSIN BOUND TO THE MINOR-GROOVE OF DNA [J].
GEIERSTANGER, BH ;
JACOBSEN, JP ;
MRKSICH, M ;
DERVAN, PB ;
WEMMER, DE .
BIOCHEMISTRY, 1994, 33 (10) :3055-3062
[6]   DESIGN OF A G-CENTER-DOT-C-SPECIFIC DNA MINOR GROOVE-BINDING PEPTIDE [J].
GEIERSTANGER, BH ;
MRKSICH, M ;
DERVAN, PB ;
WEMMER, DE .
SCIENCE, 1994, 266 (5185) :646-650
[7]   Extending the recognition site of designed minor groove binding molecules [J].
Geierstanger, BH ;
Mrksich, M ;
Dervan, PB ;
Wemmer, DE .
NATURE STRUCTURAL BIOLOGY, 1996, 3 (04) :321-324
[8]   RECOGNITION IN THE MINOR-GROOVE OF DNA AT 5'-(A,T)GCGC(A,T)-3' BY A 4-RING TRIPEPTIDE DIMER - REVERSAL OF THE SPECIFICITY OF THE NATURAL PRODUCT DISTAMYCIN [J].
MRKSICH, M ;
DERVAN, PB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1995, 117 (12) :3325-3332
[9]   ANTIPARALLEL SIDE-BY-SIDE HETERODIMER FOR SEQUENCE-SPECIFIC RECOGNITION IN THE MINOR GROOVE OF DNA BY A DISTAMYCIN 1-METHYLIMIDAZOLE-2-CARBOXAMIDE-NETROPSIN PAIR [J].
MRKSICH, M ;
DERVAN, PB .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1993, 115 (07) :2572-2576
[10]   ANTIPARALLEL SIDE-BY-SIDE DIMERIC MOTIF FOR SEQUENCE-SPECIFIC RECOGNITION IN THE MINOR GROOVE OF DNA BY THE DESIGNED PEPTIDE 1-METHYLIMIDAZOLE-2-CARBOXAMIDE NETROPSIN [J].
MRKSICH, M ;
WADE, WS ;
DWYER, TJ ;
GEIERSTANGER, BH ;
WEMMER, DE ;
DERVAN, PB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (16) :7586-7590