Cyclic Polyamides for Recognition in the Minor Groove of DNA

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 92; no. 22; pp. 10389 - 10392
• Main Authors: Cho, Junhyeong, Parks, Michelle E., Dervan, Peter B.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 24.10.1995; National Acad Sciences; National Academy of Sciences
• Subjects: Amides - chemical synthesis; Amides - chemistry; Amino acids; Base Composition; Base Sequence; Chemical bases; Chemistry; Chromatography; Deoxyribonucleic acid; Dimers; DNA; DNA - chemistry; Humans; Indicators and Reagents; Infrared radiation; Kinetics; Ligands; Microchemistry; Models, Molecular; Molecular Biology - methods; Molecular Conformation; Molecular Sequence Data; Molecules; Nucleic Acid Conformation; Nucleotide sequences; Plasmids; Pyrroles - chemical synthesis; Pyrroles - chemistry; Sensitivity and Specificity; Titration
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.92.22.10389

Small molecules that specifically bind with high affinity to any designated DNA sequence in the human genome would be useful tools in molecular biology and potentially in human medicine. Simple rules have been developed to rationally alter the sequence specificity of minor groove-binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids. Crescent-shaped polyamides bind as antiparallel dimers with each polyamide making specific contacts with each strand on the floor of the minor groove. Cyclic polyamides have now been synthesized that bind designated DNA sequences at subnanomolar concentrations.