Supramolecular ‘Glues’ for protein recognition and assembly
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Supramolecules such as calixarenes, cucurbiturils and foldamers are rapidly emerging as tools for protein assembly. This thesis builds on past successes with some of these scaffolds. Previously, sulfonato-calixarene was shown to recognize and assemble the lysine-rich cytochrome c (cytc). Here, we tested calixarenes with different upper or lower rims. A phosphonatomethyl derivative demonstrated enhanced selectivity for lysine whereas a lower rim oxomethylcarboxylate yielded a honeycomb network of cytc. A comparison of these structures highlighted how different substituents alter the recognition and the assembly-inducing behaviour. In related experiments a co-crystal structure revealed a surprising assembly of sulfonato-calixarene and a cationic porphyrin. Inspired by the interactions of calixarenes with cytc, the sulfonato-calixarene (n= 4, 6, 8) series was co-crystallized with another cationic protein – the small antifungal protein from Penicillium (PAF). It was an exciting and a rewarding project to solve the crystal structure of PAF for the first time. X-ray and solution-state studies enabled us to compare the influence of increasing calixarene size and charge on recognition and assembly. Another interesting project was to elucidate crystallographically the protein binding of a tether-free foldamer. The complex of a quinoline foldamer and cytc yielded a remarkable biohybrid assembly with chiral resolution of the foldamer helix handedness. NMR and CD experiments suggested differences in the solution state recognition processes.