Structure-activity relationships of amino glyco side-arginine conjugates that bind HIV-1 RNAs as determined by fluorescence and NMR spectroscopy

We present here a new set of aminoglycoside-arginine conjugates (AACs) that are either site-specific or per-arginine conjugates of paromomycin, neamine, and neomycin B as well as their structure-activity relationships. Their binding constants (K-D) for TAR and RRE RNAs, measured by fluorescence anisotropy, revealed dependence on the number and location of arginines in the different aminoglycoside conjugates. The binding affinity of the per-arginine aminoglycosides to TAR is higher than to RRE, and hexa-arginine neomycin B is the most potent binder (KD = 5 and 23 nM, respectively). The 2D TOCSY NMR spectrum of the TAR monoarginine-neomycin complex reveals binding at the bulge region of TAR. (C) 2004 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.