title: Synthesis and spectroscopic studies of the aminoglycoside (neomycin)--perylene conjugate binding to human telomeric DNA.
abstract: Synthesis of a novel perylene-neomycin conjugate (3) and the properties of its binding to human telomeric G-quadruplex DNA, 5'-d[AG3(T2AG3)3] (4), are reported. Various spectroscopic techniques were employed to characterize the binding of conjugate 3 to 4. A competition dialysis assay revealed that 3 preferentially binds to 4, in the presence of other nucleic acids, including DNA, RNA, DNA-RNA hybrids, and other higher-order structures (single strands, duplexes, triplexes, other G-quadruplexes, and the i-motif). UV thermal denaturation studies showed that thermal stabilization of 4 increases as a function of the increasing concentration of 3. The fluorescence intercalator displacement (FID) assay displayed a significantly tighter binding of 3 with 4 as compared to its parent constituents [220-fold stronger than neomycin (1) and 4.5-fold stronger than perylene diamine (2), respectively]. The binding of 3 with 4 resulted in pronounced changes in the molar ellipticity of the DNA absorption region as confirmed by circular dichroism. The UV-vis absorption studies of the binding of 3 to 4 resulted in a red shift in the spectrum of 3 as well as a marked hypochromic change in the perylene absorption region, suggesting that the ligand-quadruplex interaction involves stacking of the perylene moiety. Docking studies suggest that the perylene moiety serves as a bridge that end stacks on 4, making contacts with two thymine bases in the loop, while the two neomycin moieties branch into the grooves of 4.
authors.affiliation: Laboratories of Medicinal Chemistry, Clemson University, Clemson, South Carolina 29634, United States.
authors.forename: Liang
authors.initials: L
authors.lastname: Xue
authors.forename: Nihar
authors.initials: N
authors.lastname: Ranjan
authors.forename: Dev P
authors.initials: DP
authors.lastname: Arya
mesh_terms: D001483:Base Sequence; D001665:Binding Sites; D004247:DNA / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D054856:G-Quadruplexes; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D009355:Neomycin / Q000737:chemistry* / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D010569:Perylene / Q000737:chemistry* / Q000378:metabolism; D013053:Spectrophotometry / Q000379:methods*; D016615:Telomere / Q000235:genetics; D013696:Temperature
chemical_list: D010569:Perylene; D004247:DNA; D009355:Neomycin