Sequence-Specific Recognition of B-DNA by Oligo(N-methylpyrrolecarboxamide)s

• Published in: Proceedings of the National Academy of Sciences - PNAS 1985-05, Vol.82 (9), p.2565-2569
• Main Authors: Youngquist, R. Scott, Dervan, Peter B.
• Format: Article
• Language: English
• Subjects: Amides; Analytical, structural and metabolic biochemistry; Base Composition; Base Sequence; Binding Sites; Biochemistry; Biological and medical sciences; Chemical bases; Distamycins; DNA; DNA cleavage; Dna, deoxyribonucleoproteins; Fundamental and applied biological sciences. Psychology; Gels; Molecules; Netropsin; Nucleic Acid Conformation; Nucleic acids; Perceptual localization; Plasmids; Pyrroles
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.82.9.2565

Four homologous oligopeptide-EDTA molecules, tri-, tetra, penta-, and hexa(N-methylpyrrolecarboxamide)-EDTA, in the presence of Fe(II), O2, and dithiothreitol, cleave32P-end-labeled restriction fragments from plasmid pBR322 DNA at common locations rich in A· T base pairs that differ in the size of the binding site. From analysis of the cleavage patterns visualized by high-resolution denaturing gel electrophoresis, the oligopeptides with three, four, five, and six N-methylpyrrolecarboxamide units, containing four, five, six, and seven amide NHs, bind sites of A· T-rich DNA consisting of five, six, seven, and eight contiguous base pairs, respectively. The general rule of n amides affording binding site sizes of n + 1 base pairs is consistent with the oligopeptides binding in the minor groove of right-handed DNA, with the amide NH groups forming bridges between the adjacent N-3 and O-2 atoms of adenine or thymine on opposite strands of the DNA helix.