Synthesis and Biophysical Studies of High Affinity Morpholino Oligomers Containing G-clamp Analogs

Synthesis of chlorophosphoramidate morpholino monomers containing tricyclic cytosine analogs phenoxazine, G-clamp, and G8AE-clamp were achieved and incorporated into 12-mer oligonucleotides using trityl-chemistry by automated synthesizer. Phosphorodiamidate morpholino oligomers containing a single G-clamp had significantly enhanced affinity for complementary RNA and DNA relative to unmodified oligomers. The G-clamp-modified oligomers adopt a B-type helical conformation as per CD spectra. Binding affinities were sequence and position dependent.