Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow Print PDF (280K) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Right arrow Commercial Re-use Guidelines
for Open Access NAR Content
Google Scholar
Right arrow Articles by Vater, A.
Right arrow Articles by Klussmann, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Vater, A.
Right arrow Articles by Klussmann, S.
Related Collections
Right arrow Protein-nucleic acid interaction
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Nucleic Acids Research, 2003, Vol. 31, No. 21 e130
© 2003 Oxford University Press

Short bioactive Spiegelmers to migraine-associated calcitonin gene-related peptide rapidly identified by a novel approach: Tailored-SELEX

Axel Vater, Florian Jarosch, Klaus Buchner and Sven Klussmann*

NOXXON Pharma AG, Max-Dohrn-Strasse 8–10, D-10589 Berlin, Germany

*To whom correspondence should be addressed. Tel: +49 30 726247 240; Fax: +49 30 726247 243; Email: sklussmann{at}noxxon.net
The authors wish to be known that, in their opinion, the first two authors should be regarded as joint First Authors

We developed an integrated method to identify aptamers with only 10 fixed nucleotides through ligation and removal of primer binding sites within the systematic evolution of ligands by exponential enrichment (SELEX) process. This Tailored-SELEX approach was validated by identifying a Spiegelmer (‘mirror-image aptamer’) that inhibits the action of the migraine-associated target calcitonin gene-related peptide 1 ({alpha}-CGRP) with an IC50 of 3 nM at 37°C in cell culture. Aptamers are oligonucleotide ligands that can be generated to bind to targets with high affinity and specificity. Stabilized aptamers and Spiegelmers have shown activity in vivo and may be used as therapeutics. Aptamers are isolated by in vitro selection from combinatorial nucleic acid libraries that are composed of a central randomized region and additional fixed primer binding sites with ~30–40 nt. The identified sequences are usually not short enough for efficient chemical Spiegelmer synthesis, post-SELEX stabilization of aptamers and economical production. If the terminal primer binding sites are part of the target recognizing domain, truncation of aptamers has proven difficult and laborious. Tailored-SELEX results in short sequences that can be tested more rapidly in biological systems. Currently, our identified CGRP binding Spiegelmer serves as a lead compound for in vivo studies.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 Nucleic Acids ResHome page
F. Jarosch, K. Buchner, and S. Klussmann
In vitro selection using a dual RNA library that allows primerless selection
Nucleic Acids Res., July 19, 2006; 34(12): e86 - e86.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
W. G. Purschke, D. Eulberg, K. Buchner, S. Vonhoff, and S. Klussmann
An L-RNA-based aquaretic agent that inhibits vasopressin in vivo
PNAS, March 28, 2006; 103(13): 5173 - 5178.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
J. S. Mogil, F. Miermeister, F. Seifert, K. Strasburg, K. Zimmermann, H. Reinold, J.-S. Austin, N. Bernardini, E. J. Chesler, H. A. Hofmann, et al.
Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene
PNAS, September 6, 2005; 102(36): 12938 - 12943.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
D. Eulberg, K. Buchner, C. Maasch, and S. Klussmann
Development of an automated in vitro selection protocol to obtain RNA-based aptamers: identification of a biostable substance P antagonist
Nucleic Acids Res., March 3, 2005; 33(4): e45 - e45.
[Abstract] [Full Text] [PDF]

Home page
 Nucleic Acids ResHome page
J.-D. Wen and D. M. Gray
Selection of genomic sequences that bind tightly to Ff gene 5 protein: primer-free genomic SELEX
Nucleic Acids Res., December 15, 2004; 32(22): e182 - e182.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
S. Helmling, C. Maasch, D. Eulberg, K. Buchner, W. Schroder, C. Lange, S. Vonhoff, B. Wlotzka, M. H. Tschop, S. Rosewicz, et al.
Inhibition of ghrelin action in vitro and in vivo by an RNA-Spiegelmer
PNAS, September 7, 2004; 101(36): 13174 - 13179.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.