Sequence-Selective Recognition of Peptides within the Single Binding Pocket of a Self-Assembled Coordination Cage

Abstract

The single binding pocket of a self-assembled Pd₆L₄ coordination cage recognizes oligopeptides in a highly sequence-selective fashion. In particular, the Trp-Trp-Ala sequence is strongly bound by the cavity (K_a ≥10⁶ M^-1). Tripeptides possessing the same residues but in different sequences (i.e., Trp-Ala-Trp and Ala-Trp-Trp) show much poorer affinity. Even singly mutated tripeptides with aromatic−aromatic−aliphatic sequences of the residues (e.g., Trp-Trp-Gly and Trp-Tyr-Ala) are not recognized efficiently. X-ray analysis and NMR reveal that all residues of the Trp-Trp-Ala sequence cooperatively interact with the cage via CH−π and π−π interactions.