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Cucurbit[8]uril Binds Nonterminal Dipeptide Sites with High Affinity and Induces a Type II β-Turn
Paolo Suating1, Lauren B Kimberly1, Marc B Ewe1
1Department of Chemistry, Trinity University, 1 Trinity Place, San Antonio, Texas 78212, United States.
Synthetic receptor cucurbit[8]uril (Q8) effectively binds nonterminal peptide sites with high affinity. This discovery advances peptide folding applications by understanding molecular recognition and binding interactions.
Area of Science:
- Supramolecular Chemistry
- Chemical Biology
- Structural Biology
Background:
- Targeting nonterminal sites on polypeptides is challenging.
- Synthetic receptors offer novel approaches for peptide recognition.
Purpose of the Study:
- To screen and characterize synthetic receptor cucurbit[8]uril (Q8) binding to nonterminal dipeptide sites.
- To elucidate the molecular basis of Q8-peptide interactions.
Main Methods:
- Screening of a tetrapeptide library.
- Isothermal titration calorimetry (ITC).
- Nuclear Magnetic Resonance (NMR) spectroscopy.
- Mass spectrometry (MS).
- X-ray crystallography.
Main Results:
- Q8 demonstrated high affinity for nonterminal dipeptide sites Lys-Phe (KF) and Phe-Lys (FK) with dissociation constants of 60 and 86 nm, respectively.
- X-ray crystallography revealed a pair-inclusion motif involving Leu and Tyr side chains.
- Recognition involves hydrogen bonding and Q8-induced type II β-turns.
Conclusions:
- Q8 exhibits unprecedented affinity for unmodified nonterminal peptide sites.
- The detailed structural insights facilitate the design of peptide-based applications.
- This system enables ligand-induced polypeptide folding strategies.
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