Attraction by repulsion: compounds with like charges undergo self-assembly in water that improves in high salt and persists in real biological fluids

Garnett, Graham A. E.; Daze, Kevin D.; Diaz, Jorge A. Peña; Fagen, Noah; Shaurya, Alok; Manuel, C. F.; Collins, M. J.; Johnson, Darren W.; Zakharov, Lev N.; Hof, Fraser

doi:10.1039/c5cc10527g

“…Heat of dilution experiments (titration of 2–8 m m ligand into buffer) were endothermic consistent with a dissociation reaction. It was interpreted that under these conditions reversible dimerisation of the ligand was significant. Reliable data were obtained by performing a reverse titration in which, for example, 600 μ m cytochrome c was titrated into 60 μ m Br.sclx in the cell.…”

Section: Resultsmentioning

confidence: 87%

“…The Group 2 resonances (including Leu85, Lys86 and Lys87) were sigmoidal and the Hill model was used (Equation 2, see the Experimental Section). Despite reasonable agreement with these simple models the affinity estimates should be treated with caution as mono‐functionalized trisulfonato‐calixarenes can form dimers in solution . In the case of Br.sclx, the average apparent K d values were; Group 1, 0.10(±0.01) m m and Group 2, 0.19(±0.01) m m .…”

Section: Resultsmentioning

confidence: 91%

“…Two Br.sclx molecules formed a self‐encapsulated dimer (Figure A) with the bromo substituent inserted into the calixarene cavity resulting in C−Br⋅⋅⋅π halogen bonds (C−Br⋅⋅⋅centroid ≈3.3–3.9 Å). The calixarene dimer was bound to numerous lysine side chains (Figure A).…”

Section: Resultsmentioning

confidence: 99%

“…Here, we investigated the impact of mono‐functionalization on protein–calix[4]arene binding. A single sulfonate on the upper rim was substituted with a bromo (Br.sclx) or phenyl (Ph.sclx) group (Scheme ) . The interactions of these ligands with cytochrome c were studied by X‐ray crystallography, NMR spectroscopy and isothermal titration calorimetry.…”

Section: Introductionmentioning

confidence: 96%

“…While Br.sclx was observed to function similarly to sclx 4 (presenting several protein‐ligand binding sites), Ph.sclx encapsulated a single site at Lys4 suggesting altered specificity. The molecular recognition properties, ligand dimerization and halogen bonding are discussed.…”

Section: Introductionmentioning

confidence: 99%

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Protein Recognition by Functionalized Sulfonatocalix[4]arenes

Doolan

¹

,

Rennie

²

,

Crowley

³

2017

Chemistry A European J

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The interactions of two mono-functionalized sulfonatocalix[4]arenes with cytochrome c were investigated by structural and thermodynamic methods. The replacement of a single sulfonate with either a bromo or a phenyl substituent resulted in altered recognition of cytochrome c as evidenced by X-ray crystallography. The bromo-substituted ligand yielded a new binding mode in which a self-encapsulated calixarene dimer contributed to crystal packing. This ligand also formed a weak halogen bond with the protein. The phenyl-substituted ligand was bound to Lys4 of cytochrome c, in a 1.7 Å resolution crystal structure. A dimeric packing arrangement mediated by ligand-ligand contacts in the crystal suggested a possible assembly mechanism. The different protein recognition properties of these calixarenes are discussed.

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Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

Wang,

Zhang

et al. 2023

Angewandte Chemie

0

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Precise binding towards structurally similar substrates is a common feature of biomolecular recognition. However, achieving such selectivity—especially in distinguishing subtle differences in substrates—with synthetic hosts can be quite challenging. Herein, we report a novel design strategy involving the combination of different rigid skeletons to adjust the distance between recognition sites within the cavity, which allows for the highly selective recognition of hydrogen‐bonding complementary substrates, such as 4‐chromanone. X‐ray single‐crystal structures and density functional theory calculations confirmed that the distance of endo‐functionalized groups within the rigid cavity is crucial for achieving high binding selectivity through hydrogen bonding. The thermodynamic data and molecular dynamics simulations revealed a significant influence of the hydrophobic cavity on the binding affinity. The new receptor possesses both high selectivity and high affinity, which provide valuable insights for the design of customized receptors.

show abstract

Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

Wang,

Zhang

et al. 2023

View full text Add to dashboard Cite

Precise binding towards structurally similar substrates is a common feature of biomolecular recognition. However, achieving such selectivity—especially in distinguishing subtle differences in substrates—with synthetic hosts can be quite challenging. Herein, we report a novel design strategy involving the combination of different rigid skeletons to adjust the distance between recognition sites within the cavity, which allows for the highly selective recognition of hydrogen‐bonding complementary substrates, such as 4‐chromanone. X‐ray single‐crystal structures and density functional theory calculations confirmed that the distance of endo‐functionalized groups within the rigid cavity is crucial for achieving high binding selectivity through hydrogen bonding. The thermodynamic data and molecular dynamics simulations revealed a significant influence of the hydrophobic cavity on the binding affinity. The new receptor possesses both high selectivity and high affinity, which provide valuable insights for the design of customized receptors.

show abstract

Attraction by repulsion: compounds with like charges undergo self-assembly in water that improves in high salt and persists in real biological fluids

Cited by 16 publications

References 27 publications

Protein Recognition by Functionalized Sulfonatocalix[4]arenes

Protein Recognition by Functionalized Sulfonatocalix[4]arenes

Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

Precise Recognition in Water by an Endo‐Functionalized Cavity: Tuning the Complementarity of Binding Sites

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