Inhibition of Protein Aggregation by Iron Oxide Nanoparticles Conjugated with Glutamine- and Proline-Based Osmolytes

Abstract

Osmolytes are small organic biomolecules utilized by cells and organisms to counter unfavorable physiological conditions that challenge protein stability and function. Among them, some osmolytes are shown to prevent protein aggregation and act as chemical chaperones. We recently showed that nanoparticle forms of sugar-based osmolytes can enhance their chaperone performance typically by 1000–100 000 times. Here, we show that the nanoparticle form of amino acid-based osmolytes such as glutamine and proline can inhibit protein aggregation 1000–10 000 times better than respective molecular glutamine and proline. Specifically, we designed a glutamine/proline-conjugated nanoparticle with zwitterionic surface charge for best performance in inhibiting lysozyme aggregation in extracellular space and inhibiting mutant huntingtin protein aggregation in intracellular space. This result indicates that an efficient artificial chaperone can be made to inhibit protein aggregation using the nanoparticle form of osmolytes and other antiamyloidogenic molecules.