DESIGN OF A G-CENTER-DOT-C-SPECIFIC DNA MINOR GROOVE-BINDING PEPTIDE

被引:208
作者
GEIERSTANGER, BH
MRKSICH, M
DERVAN, PB
WEMMER, DE
机构
[1] CALTECH,ARNOLD & MABEL BECKMAN LABS CHEM SYNTHESIS,PASADENA,CA 91125
[2] UNIV CALIF BERKELEY,DEPT CHEM,BERKELEY,CA 94720
[3] UNIV CALIF BERKELEY,GRAD GRP BIOPHYS,BERKELEY,CA 94720
关键词
D O I
10.1126/science.7939719
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
A four-ring tripeptide containing alternating imidazole and pyrrole carboxamides specifically binds six-base pair 5'-(A,T)GCGC(A,T)-3' sites in the minor groove of DNA. The designed peptide has a specificity completely reversed from that of the tripyrrole distamycin, which binds A,T sequences. Structural studies with nuclear magnetic resonance revealed that two peptides bound side-by-side and in an antiparallel orientation in the minor groove. Each of the four imidazoles in the 2:1 ligand-DNA complex recognized a specific guanine amino group in the GCGC core through a hydrogen bond. Targeting a designated four- base pair G-C tract by this synthetic ligand supports the generality of the 2:1 peptide-DNA motif for sequence-specific minor groove recognition of DNA.
引用
收藏
页码:646 / 650
页数:5
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