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

A four-ring tripeptide containing alternating imidazole and pyrrole ca rboxamides 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 co mpletely reversed from that of the tripyrrole distamycin, which binds A,T sequences. Structural studies with nuclear magnetic resonance reve aled that two peptides bound side-by-side and in an antiparallel orien tation in the minor groove. Each of the four imidazoles in the 2:1 lig and-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 p eptide-DNA motif for sequence-specific minor groove recognition of DNA .