Noncovalent Protein-Pseudorotaxane Assembly Incorporating an Extended Arm Calix[8]arene with α-Helical Recognition Properties

Niamh M Mockler; Kiefer O Ramberg; Francesca Guagnini; Colin L Raston; Peter B Crowley

doi:10.1021/acs.cgd.0c01717

Noncovalent Protein-Pseudorotaxane Assembly Incorporating an Extended Arm Calix[8]arene with α-Helical Recognition Properties

Cryst Growth Des. 2021 Mar 3;21(3):1424-1427. doi: 10.1021/acs.cgd.0c01717. Epub 2021 Feb 8.

Authors

Niamh M Mockler¹, Kiefer O Ramberg¹, Francesca Guagnini¹, Colin L Raston², Peter B Crowley¹

Affiliations

¹ School of Chemistry, National University of Ireland Galway, University Road, Galway, H91 TK33, Ireland.
² Flinders Institute for Nanoscale Science and Technology, College of Science and Engineering, Flinders University, Bedford Park, South 5042, Australia.

Abstract

Water-soluble, anionic calix[n]arenes are useful receptors for protein recognition and assembly. For example, sulfonato-calix[8]arene (sclx ₈ ) can encapsulate proteins and direct their assembly into porous frameworks. In this work, we turned our attention to an "extended arm" calixarene with 16 phenyl rings. We hypothesized that this larger receptor would have increased capacity for protein masking/encapsulation. A cocrystal structure of p-benzyl-sulfonato-calix[8]arene (b-sclx ₈ ) and cytochrome c (cyt c) revealed a surprising assembly. A pseudorotaxane comprising a stack of three b-sclx ₈ molecules threaded by polyethylene glycol (PEG) was bound to the protein. The trimeric b-sclx ₈ stack, a tubelike structure with a highly charged surface, mediated assembly via a new mode of protein recognition. The calixarene stack presents four hydrophobic grooves, each of which binds to one cyt c by accommodating the N-terminal α-helix. This unprecedented binding mode suggests new possibilities for supramolecular protein chemistry.