Perfluoroalkane sulfonyl fluorides non-covalently bind to human serum albumin at Sudlow's sites

Toxicol Lett. 2019 Feb:301:17-23. doi: 10.1016/j.toxlet.2018.11.001. Epub 2018 Nov 5.

Abstract

Perfluorooctane sulfonyl fluoride (PFOSF) has been defined as persistent organic pollutant in the Stockholm Convention in 2009. Currently PFOSF and its substitutes (structural analogues in which octyl group is substituted for other aliphatic chains) are still scarcely studied. HSA is a main carrier for drugs in blood, and the influence of exogenous compounds including pollutants on HSA is of particular interest. In this work, the binding sites of HSA to Perfluoroalkane sulfonyl fluoride (PFASFs) were determined by fluorescence technique. The results demonstrated that PFASFs competitively bind to HSA at Sudlow's site I against warfarin and at Sudlow's site II against dansyl-proline and the related association constants were determined. The association constants of PFOSF, perfluorohexane sulfonyl fluoride (PFHSF) and perfluorobutane sulfonyl fluoride (PFBSF) were determined to be 2.59 × 10-3 μM-1, 4.65 × 10-3 μM-1 and 2.85 × 10-3 μM-1 at Sudlow's site I and 8.68 × 10-4 μM-1, 3.43 × 10-2 μM-1 and 1.92 × 10-2 μM-1 at Sudlow's site II, respectively. The results showed that PFASFs can bind tightly to HSA and thus migrate to all parts of the body through vascular system. Non-covalent interaction between HSA and PFASFs was confirmed with tryptic digestion experiment. The mass spectra results indicated that other binding sites of HSA are also involved in the binding of PFHSF and PFBSF. The total binding numbers of PFOSF, PFHSF and PFBSF on HSA are 2, 6 and 3, respectively.

Keywords: Fluorescence; HSA; MALDI; Non-covalent interaction; PFASFs.

MeSH terms

  • Binding Sites
  • Dansyl Compounds / metabolism
  • Drug Interactions
  • Fluorocarbons / metabolism*
  • Humans
  • Proline / analogs & derivatives
  • Proline / metabolism
  • Serum Albumin, Human / metabolism*
  • Sulfinic Acids / metabolism*
  • Warfarin / metabolism

Substances

  • Dansyl Compounds
  • Fluorocarbons
  • Sulfinic Acids
  • dansylproline
  • Warfarin
  • sulfuryl fluoride
  • perfluorooctane
  • Proline
  • perflexane
  • perfluorobutane
  • Serum Albumin, Human