Apoferritin and Apoferritin-Capped Metal Nanoparticles Inhibit Arginine Kinase of Trypanosoma brucei

Molecules. 2020 Jul 28;25(15):3432. doi: 10.3390/molecules25153432.

Abstract

The aim of this study was to explore the inhibitory potential of apoferritin or apoferritin-capped metal nanoparticles (silver, gold and platinum) against Trypanosomabrucei arginine kinase. The arginine kinase activity was determined in the presence and absence of apoferritin or apoferritin-capped metal nanoparticles. In addition, kinetic parameters and relative inhibition of enzyme activity were estimated. Apoferritin or apoferritin-capped metal nanoparticles' interaction with arginine kinase of T. brucei led to a >70% reduction in the enzyme activity. Further analysis to determine kinetic parameters suggests a mixed inhibition by apoferritin or apoferritin-nanoparticles, with a decrease in Vmax. Furthermore, the Km of the enzyme increased for both ATP and L-arginine substrates. Meantime, the inhibition constant (Ki) values for the apoferritin and apoferritin-nanoparticle interaction were in the submicromolar concentration ranging between 0.062 to 0.168 nM and 0.001 to 0.057 nM, respectively, for both substrates (i.e., L-arginine and ATP). Further kinetic analyses are warranted to aid the development of these nanoparticles as selective therapeutics. Also, more studies are required to elucidate the binding properties of these nanoparticles to arginine kinase of T. brucei.

Keywords: drug discovery; medicinal biochemistry; nanomedicine; selective inhibitors; trypanosomiasis.

MeSH terms

  • Apoferritins* / chemistry
  • Apoferritins* / pharmacology
  • Arginine Kinase* / antagonists & inhibitors
  • Arginine Kinase* / metabolism
  • Metal Nanoparticles* / chemistry
  • Metal Nanoparticles* / therapeutic use
  • Protozoan Proteins* / antagonists & inhibitors
  • Protozoan Proteins* / metabolism
  • Trypanocidal Agents* / chemistry
  • Trypanocidal Agents* / pharmacology
  • Trypanosoma brucei brucei / enzymology*

Substances

  • Protozoan Proteins
  • Trypanocidal Agents
  • Apoferritins
  • Arginine Kinase