Sequence-Dependent Binding of Dipeptides by an Artificial Receptor in Water

An artificial dipeptide receptor (1) was designed and observed to bind the deprotonated dipeptide Ac‐D‐Ala‐D‐Ala‐OH in buffered water with K = 33 100 m−1, whereas other dipeptides such as Ac‐Gly‐Gly‐OH or Ac‐D‐Val‐D‐Val‐OH were bound less efficiently, by factors of more than 10 (K < 3000 m−1). The efficient binding and the pronounced sequence selectivity are the result of a combination of strong electrostatic contacts and size‐discriminating hydrophobic interactions. To provide such a combination, a guanidiniocarbonylpyrrole cation was attached to a novel cyclotribenzylene‐substituted alanine derivative 5, to provide a hydrophobic bowl‐shaped cavity just large enough to bind a methyl group but not any larger alkyl chains, thus causing the receptor to prefer alanine to valine. We describe the synthesis of 1 and the evaluation of its complexation properties in UV and fluorescence titration studies. Discrimination between dipeptides: An artificial dipeptide receptor (green) is described which binds dipeptide Ac‐D‐Ala‐D‐Ala‐OH (grey) in buffered water with K = 33 100 m−1, whereas other dipeptides such as Ac‐Gly‐Gly‐OH or Ac‐D‐Val‐D‐Val‐OH are bound less efficiently, by more than a factor of 10 (K < 3000 m−1) as determined by UV and fluorescence titration studies.