Molecular recognition of N-protected dipeptides by pseudopeptidic macrocycles: a comparative study of the supramolecular complexes by ESI-MS and NMR

Abstract

The molecular recognition properties of pseudopeptidic macrocycles have been studied by ESI-MS and NMR spectroscopy, as highly complementary experimental techniques in solution and in the gas phase. We used ESI-MS competition experiments for the high throughput screening of the supramolecular interaction between four macrocyclic receptors and different peptide-like substrates in solution, rendering the best-fitted host–guest pairs. Further insights on the non-covalent recognition process in the gas-phase were obtained through collision induced dissociation (CID) experiments. Solution studies using NMR spectroscopy (¹H NMR titrations, NOESY and DOSY) were carried out to prove the validity of ESI-MS as a high-throughput screening method for studying the molecular recognition of the investigated pseudopeptidic macrocycles. A clear selectivity for N-protected dipeptides over N-protected amino acids, and a slight preference for dipeptides bearing aromatic side chains were observed. On the basis of the results obtained from this approach, a mode of binding has been proposed.