Recognition and regulation of G-quadruplex nucleic acid structures is an important goal for the development of chemical tools and medicinal agents. The addition of a bromo substituent to the dipyridylphenazine (dppz) ligands in the photophysical “light switch”, [Ru(bpy)2dppz]2+, and the photochemical “light switch”, [Ru(bpy)2dmdppz]2+, creates compounds with increased selectivity for an intermolecular parallel G-quadruplex and the mixed-hybrid G-quadruplex, respectively. When [Ru(bpy)2dppz-Br]2+ and [Ru(bpy)2dmdppz-Br]2+ are incubated with the G-quadruplexes, they have a stabilizing effect on the DNA structures. Activation of [Ru(bpy)2dmdppz-Br]2+ with light results in covalent adduct formation with the DNA. These complexes demonstrate that subtle chemical modifications of RuII complexes can alter G-quadruplex selectivity, and could be useful for the rational design of in vivo G-quadruplex probes.
Total synthesis of the anticancer peptide natural product yakuamide A is reported. Its b-tert-hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E-and Z-DIle residues was accomplished through a one-pot reaction featuring anti dehydration, azide reduction, and O!N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product.
A chemically reactive Ru(II) “building block”, able to undergo condensation reactions with substituted diamines, was utilized to create a small library of luminescent “light switch” dipyrido-[3,2-a:2′,3′-c] phenazine (dppz) complexes. The impact of substituent identity, position, and the number of substituents on the light switch effect was investigated. An unbiased, parallel screening approach was used to evaluate the selectivity of the compounds for a variety of different biomolecules, including protein, nucleosides, single stranded DNA, duplex DNA, triplex DNA, and G-quadruplex DNA. Combining these two approaches allowed for the identification of hit molecules that showed different selectivities for biologically relevant DNA structures, particularly triplex and quadruplex DNA.
Total synthesis of the anticancer peptide natural product yakuamide A is reported. Its b-tert-hydroxy amino acids were prepared by regioselective aminohydroxylation involving a chiral mesyloxycarbamate reagent. Stereospecific construction of the E-and Z-DIle residues was accomplished through a one-pot reaction featuring anti dehydration, azide reduction, and O!N acyl transfer. Alkene isomerization was negligible during this process. These methods enabled a highly convergent and efficient synthetic route to the natural product.
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