Supramolecular ‘Glues’ for protein recognition and assembly
Alex, Jimi
Alex, Jimi
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Publication Date
2019-12-06
Type
Thesis
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Abstract
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-calix[4]arene was shown to recognize and assemble the lysine-rich cytochrome c (cytc). Here, we tested calix[4]arenes 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-calix[8]arene and a cationic porphyrin. Inspired by the interactions of calixarenes with cytc, the sulfonato-calix[4]arene (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.
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NUI Galway
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Attribution-NonCommercial-NoDerivs 3.0 Ireland