posted on 2021-02-08, 16:45authored byNiamh
M. Mockler, Kiefer O. Ramberg, Francesca Guagnini, Colin L. Raston, Peter B. Crowley
Water-soluble,
anionic calix[n]arenes are useful
receptors for protein recognition and assembly. For example, sulfonato-calix[8]arene
(sclx8) 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-sclx8) and cytochrome c (cyt c) revealed a surprising assembly. A pseudorotaxane
comprising a stack of three b-sclx8 molecules threaded by polyethylene glycol (PEG) was bound
to the protein. The trimeric b-sclx8 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.