We have isolated an RNA with specific affinity for the L-valine side c
hain, using selection-amplification. The active RNA secondary structur
e, identified by repeated selection, is a highly conserved asymmetric
(4:10) internal loop adjacent to required C-U pairs. The binding free-
energy per methylene is up to 1.5 kcal mol(-1), and very dependent on
group position. Amino acid binding is L-stereoselective and distinguis
hes aliphatic sidechains by size and, given the same total size, by co
nfiguration. Though aliphatic-RNA interactions have frequently been ne
glected, their avidity and specificity seem sufficient for a biologica
l role.