Potent 2'-amino-2'-deoxypyrimidine RNA inhibitors of basic fibroblast growth factor

Biochemistry
D JellinekW A Pieken

Abstract

Screening of random oligonucleotide libraries with SELEX [systematic evolution of ligands by exponential enrichment; Tuerk, C., & Gold, L. (1990) Science 249, 505-510] has emerged as a powerful method for identifying high-affinity nucleic acid ligands for a wide range of molecular targets. Nuclease sensitivity of unmodified RNA and DNA, however, imposes considerable restrictions on their use as therapeutics or diagnostics. Modified RNA in which pyrimidine 2'-hydroxy groups have been substituted with 2'-amino groups (2'-aminopyrimidine RNA) is known to be substantially more resistant to serum nucleases. We report here on the use of SELEX to identify high-affinity 2'-aminopyrimidine RNA ligands to a potent angiogenic factor, basic fibroblast growth factor (bFGF). High-affinity ligands with the same consensus primary structure have been isolated from two independent libraries of approximately 6 x 10(14) molecules containing 30 or 50 randomized positions. Compared to unmodified RNA with the same sequence, 2'-aminopyrimidine ligands are at least 1000-fold more stable in 90% human serum. The sequence information required for high-affinity binding to bFGF is contained within 24-26 nucleotides. The minimal ligand m21A (5'-GGUGUGUGGAAGA...Continue Reading

Citations

Jan 15, 2005·Pharmaceutical Research·Judith M HealyThomas G McCauley
Jul 17, 1999·Immunopharmacology·G BieseckerR A Bendele
Oct 12, 1999·Journal of Chromatography. B, Biomedical Sciences and Applications·C E TuckerD W Drolet
Jun 1, 1996·Current Opinion in Structural Biology·K W UphoffA D Ellington
Jan 5, 1999·Bioorganic & Medicinal Chemistry Letters·S JhaveriA D Ellington
Aug 16, 2000·Journal of Biotechnology·E N Brody, L Gold
Jan 16, 2008·Accounts of Chemical Research·Steven M ShamahSharon T Cload
Jun 26, 2012·Journal of the American Chemical Society·Carmen CarrasquillaJohn D Brennan
Aug 1, 1996·Nature Biotechnology·D W DroletT S Romig
Sep 1, 1996·Nature Biotechnology·S KlussmannJ P Fürste
Sep 1, 1996·Nature Biotechnology·A NolteJ P Fürste
Aug 30, 2008·Neuropsychopharmacology : Official Publication of the American College of Neuropsychopharmacology·Errol B De SouzaDinah W Y Sah
Jun 12, 2010·Nature Protocols·Kwame SefahWeihong Tan
Jul 2, 2010·Nature Reviews. Drug Discovery·Anthony D KeefeAndrew Ellington
Aug 18, 2009·The Analyst·Kwame SefahWeihong Tan
Jun 11, 1996·Proceedings of the National Academy of Sciences of the United States of America·D O'ConnellA Varki
Feb 13, 2002·Antisense & Nucleic Acid Drug Development·C Boiziau, J J Toulmé
Dec 13, 2006·Oligonucleotides·Paula E BurmeisterAnthony D Keefe
Sep 2, 1998·Nucleic Acids Research·S M Gryaznov, H Winter
Oct 29, 2004·Nucleic Acids Research·Kathrin S SchmidtVolker A Erdmann
Oct 25, 2008·Nucleic Acids Research·Na LiAndrew D Ellington
May 9, 2003·Nucleic Acids Research·Xianbin YangDavid G Gorenstein
Oct 6, 1998·Annual Review of Biochemistry·S Verma, F Eckstein
Jun 29, 2000·Annual Review of Biochemistry·D S Wilson, J W Szostak
May 18, 2007·Annual Review of Biochemistry·S Jarrett Wrenn, Pehr B Harbury
Jan 22, 2005·Annual Review of Medicine·Shahid M NimjeeBruce A Sullenger
Oct 18, 2000·The Journal of Clinical Investigation·R R WhiteC P Rusconi
Dec 21, 2010·PloS One·Kwame SefahWeihong Tan
Jun 21, 2011·PloS One·Na LiAndrew D Ellington
Feb 24, 2012·PloS One·Harleen Kaur, Lin-Yue Lanry Yung
Oct 23, 1997·Proceedings of the National Academy of Sciences of the United States of America·K P WilliamsD P Bartel
Apr 18, 1998·Proceedings of the National Academy of Sciences of the United States of America·K N MorrisL Gold

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