Fmoc solid phase synthesis of polyamides containing pyrrole and imidazole amino acids

Polyamides containing N-methylimidazole (Im) and N-methylpyrrole (Py) amino acids are synthetic ligands that have an affinity and specificity for DNA comparable to those of many naturally occurring DNA binding proteins. A mac hine assisted Fmoc solid phase synthesis of polyamides has been optimized t o afford high stepwise coupling yields (>99%), Two monomer building blocks, Fmoc-Py acid and Fmoc-lm acid, were prepared in multigram scale. Cleavage by aminolysis followed by HPLC purification affords up to 200 mg quantities of polyamide with purities and yields greater than or equal to those repor ted using Boc chemistry, A broader set of reaction conditions will increase the number and complexity of minor groove binding polyamides which may be prepared and help ensure compatibility with many commercially available pep tide synthesizers.