Aminoglycoside hybrids as potent RNA antagonists

Aminoglycosides specifically bind to the A-site decoding region of prokaryo tic 16S rRNA with dissociation constants in the 1-2 mu M range. The aminogl ycoside paromomycin binds to a truncated A-site construct with a K-d = 1.85 mu M. Paromomycin analogs are described here in which the aminoglycoside i s linked via spacer groups to either thiazole orange or pyrene. These analo gs bind specifically to the truncated A-site construct, but with affinities considerably higher than paromomycin itself. The binding of the hybrid mol ecules to the A-site is greater the shorter the spacer group. (C) 1999 Else vier Science Ltd. All rights reserved.