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 = 33100 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.