Solid Phase Synthesis of Polyamides Containing Imidazole and Pyrrole Amino Acids

The solid phase synthesis of sequence specific DNA binding
polyamides containing N-methylimidazole
(Im) and N-methylpyrrole (Py) amino acids is described.
Two monomer building blocks, Boc-Py-OBt ester and
Boc-Im acid, are prepared on a 50 g scale without column
chromatography. Using commercially available Boc-β-alanine-Pam resin, cycling protocols were optimized to afford high
stepwise coupling yields (>99%). Deprotection
by aminolysis affords up to 100 mg quantities of polyamide. Solid
phase methodology increases both the number
and complexity of minor groove binding polyamides which can be
synthesized and analyzed with regard to DNA
binding affinity and sequence specificity. The solid phase
synthesis of a representative eight-residue polyamide is
reported.