DNA-BINDING LIGANDS FROM PEPTIDE LIBRARIES CONTAINING UNNATURAL AMINO-ACIDS

An unnatural peptide-based library bound on a solid support, was scree ned for double-stranded-DNA (dsDNA)-binding ligands. For this purpose, fluorescein and rhodamine were used to label the single-stranded olig odeoxynucleotides, Beads containing products with affinity to dsDNA tu rned red in visible light and fluoresced yellow in UV light. A similar technique can be used for the selection of ligands which bind to a ha irpin RNA, using a monolabelled oligoribonucleotide. The screening pro cess revealed a high structure-affinity relationship in the successful products, Only six out of the twelve unnatural amino acids were selec ted, with the repeated appearance of AlaU, Sar and the secondary amino acids (Hyp, Inp). The affinity and selectivity for the target was det ermined using a DNase I protection assay.