Oligomerization route to Py-Im polyamide macrocycles.
Cyclic eight-ring pyrrole-imidazole polyamides are sequence-specific DNA-binding small molecules that are cell permeable and can regulate endogenous gene expression. Syntheses of cyclic polyamides have been achieved by solid-phase and solution-phase methods. A rapid solution-phase oligomerization approach to eight-ring symmetrical cyclic polyamides yields 12- and 16-membered macrocycles as well. A preference for DNA binding by the 8- and 16-membered oligomers was observed over the 12-ring macrocycle, which we attributed to a conformational constraint not present in the smaller and larger systems.
Chenoweth
David M
DM
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA.
Harki
Daniel A
DA
Dervan
Peter B
PB
D001483:Base Sequence; D004247:DNA / Q000737:chemistry; D007093:Imidazoles / Q000737:chemistry*; D015394:Molecular Structure; D009757:Nylons / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000737:chemistry*
D007093:Imidazoles; D009757:Nylons; D011758:Pyrroles; D004247:DNA