HIGH-AFFINITY RNA LIGANDS TO BASIC FIBROBLAST GROWTH-FACTOR INHIBIT RECEPTOR-BINDING

We have isolated RNA ligands with low-nanomolar affinity and high spec ificity to basic fibroblast growth factor from a pool of 10(14) molecu les containing 30 randomized positions by the systematic evolution of ligands by exponential enrichment (SELEX) procedure. High-affinity lig ands could be classified into two families based on sequence and secon dary structure similarities. Representative RNA ligands from the two f amilies compete with one another as well as with heparin for binding t o the protein. Furthermore, we show that these ligands inhibit the fir st step in the signaling pathway of basic fibroblast growth factor: bi nding of the growth factor to its cell-surface receptors. These findin gs emphasize the general usefulness of SELEX as a tool for discovering potent, specific oligonucleotide antagonists of target proteins.