Interaction of cyclosporin A with an Fab fragment or cyclophilin. Affinity measurements and time-dependent changes in binding

FEBS Lett. 1993 Jul 12;326(1-3):153-7. doi: 10.1016/0014-5793(93)81781-t.

Abstract

Different conformers of the immunosuppressant cyclosporin A have been observed in structural studies of the isolated molecule and of its complex with cyclophilin or with an Fab fragment. The factors that control this conformational change are not well understood. Variations in the amount of complex formed with cyclophilin or with the antibody were measured as a function of time after adding cyclosporin to the proteins, using the Pharmacia BIAcore biosensor instrument. Up to 1 hour was needed to reach maximum complex formation in solution, which is likely to reflect the time needed for a conformational transition of cyclosporin. The equilibrium affinity constant of both proteins for cyclosporin has been measured.

MeSH terms

  • Amino Acid Isomerases / metabolism*
  • Antibodies, Monoclonal / metabolism
  • Antibody Affinity
  • Carrier Proteins / metabolism*
  • Cyclosporine / chemistry
  • Cyclosporine / immunology
  • Cyclosporine / metabolism*
  • Immunoglobulin Fab Fragments / metabolism*
  • Kinetics
  • Molecular Conformation
  • Peptidylprolyl Isomerase
  • Solutions

Substances

  • Antibodies, Monoclonal
  • Carrier Proteins
  • Immunoglobulin Fab Fragments
  • Solutions
  • Cyclosporine
  • Amino Acid Isomerases
  • Peptidylprolyl Isomerase