RNA MOLECULES THAT BIND TO AND INHIBIT THE ACTIVE-SITE OF A TYROSINE PHOSPHATASE

Protein tyrosine phosphatases (PTPases) are essential proteins in many cellular processes. In vitro selection was used to evolve high affini ty RNA aptamers to the Yersinia PTPase from two random pools varying i n length. Selected aptamers from the two different pools share a 21-re sidue conserved sequence. They bind to their target with dissociation constants of 18 and 28 nM and inhibit the enzyme with IC50 values of 1 0 and 35 nM, but do not bind a related PTPase. Modification of the PTP ase's active site cysteine with the alkylating agent iodoacetate resul ts in a loss of binding affinity. These experiments suggest that the s elected aptamers act by binding at or near the active site and might t herefore be useful in defining the interactions between PTPases and th eir targets.