title: GnRH binding RNA and DNA Spiegelmers: a novel approach toward GnRH antagonism.
abstract: Mirror-image oligonucleotide ligands (Spiegelmers) that bind to the pharmacologically relevant target gonadotropin-releasing hormone I (GnRH) with high affinity and high specificity have been identified using the Spiegelmer technology. GnRH is a decapeptide that plays an important role in mammalian reproduction and sexual maturation and is associated with several benign and malignant diseases. First, aptamers that bind to D-GnRH with dissociation constants of 50-100 nM were isolated out of RNA and DNA libraries. The respective enantiomers of the DNA and RNA aptamers were synthesized, and their binding to L-GnRH was shown. These Spiegelmers bind to L-GnRH with similar affinity to that of the corresponding aptamers that bind to D-GnRH. We further demonstrated dose-dependent inhibition of GnRH-induced Ca(2+) release in Chinese hamster ovary cells that were stably transfected with the human GnRH receptor.
authors.affiliation: NOXXON Pharma AG, Gustav-Meyer-Allee 25, D-13355 Berlin, Germany.
authors.forename: Susanne
authors.initials: S
authors.lastname: Leva
authors.forename: Andrea
authors.initials: A
authors.lastname: Lichte
authors.forename: Jens
authors.initials: J
authors.lastname: Burmeister
authors.forename: Peter
authors.initials: P
authors.lastname: Muhn
authors.forename: Birgit
authors.initials: B
authors.lastname: Jahnke
authors.forename: Dirk
authors.initials: D
authors.lastname: Fesser
authors.forename: Jeannette
authors.initials: J
authors.lastname: Erfurth
authors.forename: Petra
authors.initials: P
authors.lastname: Burgstaller
authors.forename: Sven
authors.initials: S
authors.lastname: Klussmann
mesh_terms: D000818:Animals; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques; D006224:Cricetinae; D017931:DNA Primers; D015723:Gene Library; D007987:Gonadotropin-Releasing Hormone / Q000037:antagonists & inhibitors*; D006801:Humans; D008024:Ligands; D009841:Oligonucleotides / Q000494:pharmacology* / Q000627:therapeutic use; D017422:Sequence Analysis, DNA; D017423:Sequence Analysis, RNA
chemical_list: D017931:DNA Primers; D008024:Ligands; D009841:Oligonucleotides; D007987:Gonadotropin-Releasing Hormone