DNA-binding polyamides

The amino acid 58 was used in the solid-phase synthesis of sequence-specific DNA binding polyamides containing N-methylimidazole and N-methylpyrrole amino acids <96JACS6141> and it was also reported that the imidazole-acridine conjugate 59 could effectively catalyze the cleavage of t-RNA <96TL4417>. 

The availability of sequence-specific DNA binding molecules led to the development of bifunctional polyamides that covalently react with the minor groove of DNA. Two classes of alkylating agents were conjugated to the hairpin turn unit and bound proximal to their alkylation sites by a DNA-binding polyamide [58, 59]. 

C. Melander, P.B. Dervan, and D.M. Crothers. Kinetic consequences of covalent linkage of DNA binding polyamides. Biochemistry 2001, 40, 3-8. 

Belitsky, J.M., D. H. Nguyen, N. R. WuRTZ, and P. B. Dervan. Solid-phase synthesis of DNA binding polyamides on oxime resin. Bioorg. Med. Chem. 2002,... 

This field has also inspired the development of a range of pseudo-peptides, that is polyamides composed of amino acids other than a-amino acids. These include for instance peptoids, /9-amino acid oligomers and also compounds such as peptide nucleic acids and DNA binding polyamides, all of which share the amide (peptide) chemistry with natural peptides. 

Dudouet B, Burnett R, Dickinson LA, Wood MR, Melander C, Belitsky JM, Edelson B, Wurtz N, Briehn C, Dervan PB, Gottesfeld JM (2003) Accessibility of nuclear chromatin by DNA binding polyamides. Chem Biol 10 859-867... 

Nickols NG, Jacobs CS, Farkas ME, Dervan PB. Improved nuclear localization of DNA-binding polyamides. Nucleic Acids Res. 2007 35 363-370. 

---