NDLI: In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class.

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In vivo properties of an anti-GnRH Spiegelmer: an example of an oligonucleotide-based therapeutic substance class.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Kleinjung, Frank Eschgfäller, Bernd Wlotzka, Britta Hess-stumpp, Holger Muhn, Peter Burmeister, Jens Kaduk, Christine Leva, Susanne Klussmann, Sven
Description	Author Affiliation: Wlotzka B ( NOXXON Pharma AG, Gustav-Meyer-Allee 25, 13355 Berlin, Germany.);
Abstract	Spiegelmers are high-affinity l-enantiomeric oligonucleotide ligands that display high resistance to enzymatic degradation compared with d-oligonucleotides. The target binding properties of Spiegelmers can be designed by an in vitro-selection process starting from a random pool of oligonucleotides. Applying this method, a Spiegelmer with high affinity (K(D) = 20 nM) for the peptide hormone, gonadotropin-releasing hormone (GnRH) was isolated. The Spiegelmer acts as an antagonist to GnRH in Chinese hamster ovary cells stably expressing the human GnRH receptor, and its activity is unchanged by linking to 40-kDa polyethylene glycol. In a castrated rat model the Spiegelmer further demonstrated strong GnRH antagonist activity, which is more pronounced and persists longer with the polyethylene glycol-linked derivative. Furthermore, in rabbits the anti-GnRH Spiegelmer was shown to have a very low, possibly negligible immunogenic potential. These studies suggest that Spiegelmers could be of substantial interest in the development of new pharmaceutical approaches against GnRH and other targets.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	13
Volume Number	99
Language	English
Publisher	National Academy of Sciences
Publisher Date	2002-06-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Gonadotropin-Releasing Hormone Antagonists & Inhibitors Oligonucleotides Pharmacology Animals CHO Cells Cricetinae DNA Primers Therapeutic Use Rabbits Research Support, Non-U.S. Gov't Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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