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A Closed Cavity Strategy for Selective Dipeptide Binding by a Polyaromatic Receptor in Water

Mayu Shuto, Ryuki Sumida, Mana Yuasa, Tomohisa Sawada, Michito Yoshizawa

2023JACS Au13 citationsDOIOpen Access PDF

Abstract

High Resolution Image Download MS PowerPoint Slide Precise recognition of peptides is a daunting task owing to the substantial number of available amino acids and their combination into various oligo/polymeric structures in addition to the high hydration of their flexible frameworks. Here, we report the selective recognition of a dipeptide through a closed cavity strategy, in contrast to previous synthetic receptors with open cavities. A polyaromatic receptor with a virtually isolated, hydrophobic cavity exclusively binds one molecule of phenylalanine dipeptide from a mixture with its amino acid and tripeptide in water via multiple CH−π and hydrogen-bonding interactions in the complementary cavity. The binding selectivity persists even in the presence of other dipeptides, such as leucine–leucine, leucine–phenylalanine, tyrosine–phenylalanine, tryptophan–tryptophan, and aspartame, revealed by NMR/MS-based competitive binding experiments. ITC studies reveal that the selective binding of the phenylalanine dipeptide is relatively strong ( K a = 1.1 × 10 5 M –1 ) and an enthalpically and entropically favorable process (Δ H = −11.7 kJ mol –1 and T Δ S = 17.0 kJ mol –1 ). In addition, the present receptor can be used for the emission detection of the dipeptide through a combination with a fluorescent dye in water.

Topics & Concepts

DipeptideChemistryReceptorBiophysicsCombinatorial chemistryStereochemistryPeptideBiochemistryBiologyMolecular Sensors and Ion DetectionLuminescence and Fluorescent MaterialsSupramolecular Chemistry and Complexes