Chiral adaptive recognition with sequence specificity of aromatic dipeptides in aqueous solution by an achiral cage.

Abstract

Sequence-specific recognition of peptides and proteins by synthetic compounds or systems remains a huge challenge in biocompatible media. Here, we report the chiral adaptive recognition (CAR) with sequence specificity of aromatic dipeptides in a purely aqueous solution using an achiral tetraphenylethene-based octacationic cage (1) as both a molecular receptor and chiroptical sensor. 1 can selectively bind and dimerize aromatic dipeptides to form 1 : 2 host-guest complexes with high binding affinity (>1010 M-2), especially up to ∼1014 M-2 for TrpTrp. Given the dynamic rotational conformation of TPE units, achiral 1 can exhibit chiral adaptive responses with mirror-symmetrical circular dichroism (CD) and circularly polarized luminescence (CPL) spectra to enantiomeric dipeptides via supramolecular chirality transfer in the host-guest complexes. Furthermore, this CAR with sequence specificity of 1 can be applied for molecular recognition of TrpTrp- or PhePhe-containing tetrapeptides, polypeptides (e.g., amyloid β-peptide1-20 and somatostatin), and proteins (e.g., human insulin) with characteristic CD responses.