Large Increase in Cation Binding Affinity of Artificial Cyclopeptide Receptors by an Allosteric Effect

The receptor properties of a cyclopeptide composed of l -glutamic acid and 3-aminobenzoic acid in an alternating sequence are described. 1 H NMR, NOESY NMR, and FT-IR spectroscopic investigations show that this cyclic peptide is relatively flexible in solution. Still, it is able to bind cations by cation−π interactions. For the n -butyltrimethylammonium iodide complex, for example, an association constant of 300 M - 1 has been determined in chloroform. Besides cations, the cyclopeptide is also able to bind certain anions, such as sulfonates or phosphonates, at a second binding site. NMR and FT-IR spectroscopic investigations show that these anions are hydrogen bonded to the peptidic NH groups. Anion complexation results in an increase of the cyclic peptide's cation affinity by a factor of 10 3 −10 4 . The cyclopeptide−tosylate complex structure in solution was assigned by FT-IR, 1 H NMR, and NOESY NMR spectroscopic methods as well as molecular modeling. This structure shows that the drastic increase in cation binding affinity can be correlated with a preorganization of the cyclic peptide by the anion as well as electrostatic interactions between anion and cationic substrates in the final complex. Therefore, the influence of the anions on the complexing behavior of the cyclopeptide can be regarded as an allosteric effect . Association constants of the K + −18-crown-6, Na + −15-crown-5, and n -butyltrimethylammonium cation complexes have been determined by dilution and competitive NMR titrations.