An RNA pocket for the planar aromatic side chains of phenylalanine and tryptophane

This is a preliminary report of RNA's with affinity for the aromatic side chains of the amino acids phenylalanine and tryptophane that have been isolated utilizing in vitro selection to phenylalanine-affinity matrix. Cloning and sequencing of a binding pool identified a frequently occurring 6-9 base motif (-CUCGUGU-) common to most of the RNA's; other potential binding motifs were revealed but occurred less frequently. Four of five clones analyzed bind free phenylalanine and tryptophane with dissociation constants in the low millimolar range, the fifth binds resin only. Isolate F7, the most common sequence in the binding pool, demonstrated moderate specificity for aromatic rings, no stereoselectivity was observed. Preliminary Pb cutting structural analysis agrees with the most stable predicted secondary structure. A striking similarity between the sequence and predicted structure of F7 and the bridged-biphenylisomerase RNA (J.R. Prudent, T. Uno, and P.G. Schultz, Science 264,1924 (1994)) suggests a 19 base loop contains the important aromatic binding elements.