Combinatorial libraries of diamidopyridine-derived ‘tweezer’ receptors and sequence selective binding of peptides

A library of diamidopyridine derived tweezer receptors with peptidic side-arms has been prepared. Screening experiments with the library and a dye-labelled tripeptide l-Glu–l-Ser–l-Val–OH showed excellent selectivity (strong binding of the dye-labelled guest to ∼0.2% of resin-bound library members was observed) and led to the identification of a tweezer receptor structure, which was shown to bind the tripeptide with good selectivity over related tripeptide sequences. Analogous screening experiments with the side-chain protected tripeptide l-Glu(OtBu)–l-Ser(tBu)–l-Val–OH, showed little selectivity for any particular library member. The results are discussed in relation to previous screening experiments, using the same tripeptide guests, with related tweezer receptor libraries, which differ by one methylene in the separation of the diamidopyridine unit from the peptidic side-arms of the tweezer receptors.