Harnessing non-covalent interactions for peptide encapsulation within metal-organic materials Imogen Riddell, Xiangyu Wang, Tongtong Zhang, Jonathan Robson, Maria Giovanna Lizio, Daniel Bell, Jack Wright University of Manchester, UK Metal-organic containers have shown utility in diverse applications from gas storage to catalysis, 1 however their application within biological contexts remains in its infancy. We are interested in exploiting the unique internal environments of porous metal-organic materials to better understand the effects of protein constriction. Enzymes exhibit high catalytic efficiency and specificity making them desirable candidates for application in biotechnology settings. However, the inherent fragility of these structures arising from their tendency to become denatured following exposure to moderate temperature or pH changes, and organic solvents remains a major drawback. Materials capable of reinforcing the three-dimensional structure of proteins and preventing loss of catalytic activity (and possibly even enhancing it) 2 are highly desirable. Factors governing the spontaneous biomimetic crystallization 3 of MOFs around proteins will be discussed as well as techniques for characterisation of these hybrid materials. Synthesis and characterisation of metal-organic cages displaying sequence selective binding of short peptides directed by non-covalent interactions will also be presented. Evaluation of peptide binding within well-defined void pockets, which can be tailored, provides a route to understand the effects crowded cellular environments 4 have on peptide folding. Such synthetic complexes may ultimately guide the design of capsules capable of directing refolding of un/misfolded peptide sequences. 5 References 1. N.Ahmad,H. A. Younus,A. H. Chughtai, F. Verpoort, Chem. Soc. Rev . , 2015, 44 , 9. 2. K. Liang, R. Ricco, C. M. D., M. J. Styles, S. Bell, N. Kirby, S. Mudie, D. Haylock, A. J. Hill, C. J. Doonan, P. Falcaro, Nat. Commun ., 2015, 6 , 7240. 3. J. Liang, M. Y. B. Zulkifli, J. Yong, Z. Du, Z. Ao, A. Rawal, J. A. Scott, J. R. Harmer, J. Wang, K. Liang, J. Am. Chem. Soc, 2022, 144 , 17865. 4. A. P. Minton, J. Biol.Chem ., 2001, 276 , 10577. T. Nishimura, K. Akiyoshi, Bioconjugate Chem. 2020, 31 , 1259.
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