High-affinity RNA ligands to basic fibroblast growth factor inhibit receptor binding.
We have isolated RNA ligands with low-nanomolar affinity and high specificity to basic fibroblast growth factor from a pool of 10(14) molecules containing 30 randomized positions by the systematic evolution of ligands by exponential enrichment (SELEX) procedure. High-affinity ligands could be classified into two families based on sequence and secondary structure similarities. Representative RNA ligands from the two families compete with one another as well as with heparin for binding to the protein. Furthermore, we show that these ligands inhibit the first step in the signaling pathway of basic fibroblast growth factor: binding of the growth factor to its cell-surface receptors. These findings emphasize the general usefulness of SELEX as a tool for discovering potent, specific oligonucleotide antagonists of target proteins.
Jellinek
D
D
NeXagen, Inc., Boulder, CO 80301.
Lynott
C K
CK
Rifkin
D B
DB
Janjić
N
N
D001483:Base Sequence; D016384:Consensus Sequence; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006860:Hydrogen Bonding; D008024:Ligands; D008969:Molecular Sequence Data; D009690:Nucleic Acid Conformation; D009843:Oligoribonucleotides / Q000737:chemistry; D012313:RNA / Q000378:metabolism*; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D013329:Structure-Activity Relationship
D008024:Ligands; D009843:Oligoribonucleotides; D016222:Fibroblast Growth Factor 2; D012313:RNA