Supramolecular ‘Glues’ for protein recognition and assembly

Alex, Jimi
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.
NUI Galway
Publisher DOI
Attribution-NonCommercial-NoDerivs 3.0 Ireland