Host-Guest Induced Peptide Folding with Sequence-Specific Structural Chirality.

David E Clarke,Ce Wu,Guanglu Wu,Oren A Scherman

doi:10.1021/jacs.1c00342

David E Clarke, Ce Wu + Show 2 more

Open Access

https://doi.org/10.1021/jacs.1c00342

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Abstract

Controlling the spatial and temporal behavior of peptide segments is essential in the fabrication of functional peptide-based materials and nanostructures. To achieve a desired structure, complex sequence design is often required, coupled with the inclusion of unnatural amino acids or synthetic modifications. Herein, we investigate the structural properties of 1:1 inclusion complexes between specific oligopeptides and cucurbit[8]uril (CB[8]), inducing the formation of turns, and by alteration of the peptide sequence, tunable structural chirality. We also explore extended peptide sequence binding with CB[8], demonstrating a simple approach to construct a peptide hairpin.

Highlights

Controlling the spatial and temporal behavior of peptide segments is essential in the fabrication of functional peptidebased materials and nanostructures
Two adjacent side chains of the peptide simultaneously reside inside the cavity, resembling a ternary motif but with the exception that the encapsulated moieties are connected via a covalent amide bond.24−26 This binding motif exhibits a host-mediated adjacent side-chain pairing (HASP), which we have termed a “HASP knot”, representing a pseudostatic complexation tecton
Through utilizing circular dichroism (CD) spectroscopy, we identified that the formation of HASP knots can induce a significant conformational change

Summary

Introduction

Controlling the spatial and temporal behavior of peptide segments is essential in the fabrication of functional peptidebased materials and nanostructures. In line with previous studies on tripeptides,24,25 isothermal titration calorimetry and NMR experiments revealed that Y residues coupled with an aliphatic amino acid (YL/LY, YM/ MY, YK/KY) or an additional Y residue (YY) were all found to favor the formation of HASP knots (Figures S2−S9).26 The CD spectra of these dipeptides display similar CD signatures, with minima around 190 nm and positive inflections at 200 and 225 nm (Figure 1c).

Results

Conclusion