Ch. Wong et al., A LIBRARY APPROACH TO THE DISCOVERY OF SMALL MOLECULES THAT RECOGNIZERNA - USE OF A 1,3-HYDROXYAMINE MOTIF AS CORE, Journal of the American Chemical Society, 120(33), 1998, pp. 8319-8327
A library of compounds based upon an aminoglucopyranoside core has bee
n developed and screened for binding to RNA and specifically to 16S ri
bosomal RNA. The title molecules simplify the complexity of naturally
occurring aminoglycoside antibiotics by embodying a putative recogniti
on motif found within these structures, namely, a 1,3-hydroxyamine. Th
e core pyranoside bearing the hydroxyamine motif was structurally vari
ed at two points through a combinatorial approach utilizing acylation
and reductive amination protocols. The aminoglycoside mimetics were sc
reened in an automated assay based upon surface plasmon resonance (SPR
), and some were found effective at binding a 27-nucleotide model (AS-
wt) of A-site 16S RNA as well as a drug-resistant mutant RNA in the mi
cromolar range.