RNA APTAMERS THAT SPECIFICALLY BIND TO A K-RAS-DERIVED FARNESYLATED PEPTIDE

RNA aptamers were selected against an affinity column containing a far nesylated peptide modeled after the carboxyl terminus of K ras, the ma jor oncogenic form of this small G protein family. After 10-rounds of selection, 25% of the RNA applied to the column could be specifically eluted. Sequence analysis of the binding RNA aptamers revealed two con sensus sequences-GGGUGGG and GGGAGG. Quantitative fluorescence binding studies on two of the high-affinity aptamers, showed a binding affini ties of 139 nM and 0.93 mu M, respectively for the farnesylated peptid e. Binding to the nonfarnesylated peptide was at least 10-fold weaker, showing that the aptamers can recognize the hydrophobic farnesyl moie ty. High affinity aptamers could be useful in specifically interfering with oncogenic ras function in particular, and G proteins in general. (C) 1997 Elsevier Science Ltd.