6533b7d1fe1ef96bd125d7c6
RESEARCH PRODUCT
The size of aryl linker between two polyaza-cyclophane moieties controls the binding selectivity to ds-RNA vs ds-DNA
Enrique García-españaLidija UzelacJorge González-garcíaMarijeta KraljJosé M. LlinaresIvo Piantanidasubject
Aza CompoundsBinding SitesMolecular StructureStereochemistryChemistryPyridinesDimerOrganic ChemistryRNADNABiochemistrypolyaza-cyclophane ; DNA ; RNA ; selectivity ; antiproliferative activitychemistry.chemical_compoundPolynucleotidePhysical and Theoretical ChemistryBinding siteParticle SizeLinkerBinding selectivityDNACyclophanePhenanthrolinesRNA Double-Strandeddescription
Aryl-linked (pyridine- vs. phenanthroline-) bis-polyaza pyridinophane scorpiands PYPOD and PHENPOD strongly bind to the double stranded DNA and RNA, whereby very intriguing RNA over DNA selectivity is finely tuned by aryl-linker length and aromatic surface. Moreover, PYPOD and PHENPOD dimer formation at high compound/polynucleotide ratios is highly sensitive to the fine interplay between the steric and binding properties of compound-dimers and the DNA minor groove/RNA major groove. That is demonstrated by significantly different induced CD spectra, which allow spectroscopic differentiation between various DNA/RNA secondary structures. A significantly higher (micromolar) antiproliferative effect of PYPOD and PHENPOD on human cell lines with respect to previously reported pyridine-based tripodal aliphatic polyamines is attributed to masked positive charges and increased hydrophobicity of novel compounds, resulting in more efficient membrane permeation and cellular uptake.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2013-02-09 |