title: d(GGGT) 4 and r(GGGU) 4 are both HIV-1 inhibitors and interleukin-6 receptor aptamers.
abstract: Aptamers are oligonucleotides that bind targets with high specificity and affinity. They have become important tools for biosensing, target detection, drug delivery and therapy. We selected the quadruplex-forming 16-mer DNA aptamer AID-1 [d(GGGT) 4] with affinity for the interleukin-6 receptor (IL-6R) and identified single nucleotide variants that showed no significant loss of binding ability. The RNA counterpart of AID-1 [r(GGGU) 4] also bound IL-6R as quadruplex structure. AID-1 is identical to the well-known HIV inhibitor T30923, which inhibits both HIV infection and HIV-1 integrase. We also demonstrated that IL-6R specific RNA aptamers not only bind HIV-1 integrase and inhibit its 3' processing activity in vitro, but also are capable of preventing HIV de novo infection with the same efficacy as the established inhibitor T30175. All these aptamer target interactions are highly dependent on formation of quadruplex structure.
authors.affiliation: Institute for Biochemistry and Molecular Biology, Chemistry Department, MIN-Faculty, Hamburg University, Hamburg, Germany.
authors.forename: Eileen
authors.initials: E
authors.lastname: Magbanua
authors.forename: Tijana
authors.initials: T
authors.lastname: Zivkovic
authors.forename: Björn
authors.initials: B
authors.lastname: Hansen
authors.forename: Niklas
authors.initials: N
authors.lastname: Beschorner
authors.forename: Cindy
authors.initials: C
authors.lastname: Meyer
authors.forename: Inken
authors.initials: I
authors.lastname: Lorenzen
authors.forename: Joachim
authors.initials: J
authors.lastname: Grötzinger
authors.forename: Joachim
authors.initials: J
authors.lastname: Hauber
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Torda
authors.forename: Günter
authors.initials: G
authors.lastname: Mayer
authors.forename: Stefan
authors.initials: S
authors.lastname: Rose-John
authors.forename: Ulrich
authors.initials: U
authors.lastname: Hahn
mesh_terms: D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D002942:Circular Dichroism; D004353:Drug Evaluation, Preclinical; D054856:G-Quadruplexes / Q000187:drug effects; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000473:pathology / Q000821:virology; D019427:HIV Integrase / Q000235:genetics / Q000378:metabolism; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000472:pathogenicity; D006367:HeLa Cells; D006801:Humans; D009841:Oligonucleotides / Q000494:pharmacology; D019947:Receptors, Interleukin-6 / Q000378:metabolism*; D053585:Virus Attachment / Q000187:drug effects
chemical_list: D052157:Aptamers, Nucleotide; D015699:HIV Envelope Protein gp120; D019428:HIV Integrase Inhibitors; C508603:IL6R protein, human; D009841:Oligonucleotides; D019947:Receptors, Interleukin-6; C545001:T30923; C514793:gp120 protein, Human immunodeficiency virus 1; D019427:HIV Integrase