Aminoglycoside-quinacridine conjugates: Towards recognition of the P6.1 element of telomerase RNA
ChemBioChem. 2006-01-12; 7(2): 321-329
DOI: 10.1002/cbic.200500354
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1. Chembiochem. 2006 Feb;7(2):321-9.
Aminoglycoside-quinacridine conjugates: towards recognition of the P6.1 element
of telomerase RNA.
Kaiser M(1), Sainlos M, Lehn JM, Bombard S, Teulade-Fichou MP.
Author information:
(1)Laboratoire de Chimie des Interactions Moléculaires, CNRS UPR 285, Collège de
France.
A modular synthesis has been developed which allows easy and rapid attachment of
one or two aminoglycoside units to a quinacridine intercalator, thereby leading
to monomeric and dimeric conjugates. Melting temperature (Tm) experiments show
that the tobramycin dimeric conjugate TD1 exhibits strong binding to the P6.1
element of human telomerase RNA. By contrast, tobramycin alone is much less
efficient and the monomeric compound TM1 elicits a poor binding ability.
Monitoring of the interaction by an electrophoretic mobility shift assay shows a
1:1 stoichiometry for the binding of the dimeric compound to the hairpin
structure and confirms the lower affinity for a control duplex. Protection
experiments with RNase T1 indicate interaction of the drug both in the stem and
in the loop of the hairpin. Taken together, the data suggest a binding of TD1
inside the hairpin at the stem-loop junction. The same trends are observed with
paromomycin and kanamycin analogues but with a lower affinity.
DOI: 10.1002/cbic.200500354
PMID: 16408312 [Indexed for MEDLINE]