Discovery of selective metal-binding peptoids using 19F encoded combinatorial libraries

A method for encoding solid-phase split/mix combinatorial libraries using the chemical shift of synthetic fluoroarenes (‘F-codes’) has been developed. They have wide chemical shift dispersion and are detectable at the sub-μmol level. 19F NMR is used for decoding. Nine fluoroarenes bearing linkers for attachment to solid-phase synthesis supports through a photocleavable group were prepared. A library of 90 N-alkylglycines bearing substituted succinamides was prepared on solid phase from nine amines, in which the amine is encoded by the fluorinated tag, and 10 anhydrides. Metal binding studies followed by decoding identified unique, specific binders of copper(II) and iron(III) with μM KDs.