A route for preparing new neamine derivatives targeting HIV-1 TAR RNA

Abstract

In the search for molecules possessing antibiotic or antiviral properties and ribonuclease like activity, that is, able to induce the cleavage of bacterial or viral RNA targets, we report a new route for preparing selectively neamine derivatives modified at their 4′- and/or 5-hydroxyl functions. Using trityl protective groups for the amino functions and 4-methoxybenzyl groups for the hydroxyl functions, new neamine derivatives, such as histidine, phenanthroline, flavin, adenine conjugates were efficiently obtained after a single deprotection step under acid conditions. For the first time, 4′-modified neamine derivatives were prepared. Most of the 4′-derivatives showed affinity and selectivity for TAR RNA close to those of the corresponding 5-derivatives. The most potent compound is the 4′-histidine derivative 31 which binds more tightly to TAR RNA compared to its 5-isomer and neamine and recognizes selectively TAR oligonucleotides having a bulge.