Harnessing the Dynamic Nature of a Zirconium‐Oxo Nanocluster for Reversible Protein Capture and Proteolysis

Authors:
Publisher website
Google Scholar
Abstract
Selective proteolysis remains a significant challenge with relevance to industrial and pharmaceutical applications, motivating development of chemical strategies emulating the specificity of natural proteases. Here, we report that the discrete Zr‐oxo nanocluster‐based solid, [Zr17O8(OH)24(OH2)12(HCO2)12(SO4)8] · 6 HCl · 30 H2O (Zr17) serves as an efficient, recyclable heterogeneous catalyst for site‐selective proteolysis with tunable fragment selectivity. A combination of solution‐ and solid‐state NMR spectroscopy highlighted the importance of the ligand environment of solid Zr17 for enabling efficient protein‐cluster interaction and controlling reactivity. We demonstrate that Zr17 achieves a proteolytic performance comparable to natural enzymes while allowing fine modulation of peptide product profiles by adjusting reaction parameters. Substrate adsorption and product desorption were found to be governed by the net charge of both catalyst and substrate, as well as rapid reorganization of the cluster's capping ligands, according to UV‐Vis/IR spectroscopy and isothermal titration calorimetry. Crucially, the insoluble nature and excellent stability of Zr17, evidenced by pair distribution function analysis, allowed reuse across multiple catalytic cycles, overcoming a major limitation of proteolytic systems. This study reveals how cluster surface chemistry governs substrate interaction and catalysis, guiding rational design of next‐generation cluster‐based catalysts, including hybrid materials such as metal‐organic frameworks.
Funding Information
  • KU Leuven (C14/23/088, CELSA/24/007)
  • Fonds Wetenschappelijk Onderzoek (G025624N, I002720N)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (194172, 218106)

This publication has 49 references indexed in Scilit: