A study of the correlation between cyclophilin binding and in vitro immunosuppressive activity of cyclosporine A and analogues

Transplant Proc. 1988 Apr;20(2 Suppl 2):51-7.

Abstract

In order to establish whether CyP is the pharmacologically relevant CsA receptor, the CyP binding v immunosuppressive activity was measured for an extensive, structurally varied group of CsA analogues. Overall, CyP binding was found to parallel immunosuppressive activity. Other than MeAla6-CsA, the few exceptions to the correlation could be ascribed to cellular metabolism. These results strongly implicate CyP or a related protein in the mechanism of action of cyclosporine.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism*
  • Cyclosporins / metabolism*
  • Ethers / pharmacology
  • Immunosuppression Therapy*
  • Immunosuppressive Agents*
  • In Vitro Techniques
  • Interleukin-2 / metabolism
  • Ionomycin
  • Lymphocyte Activation / drug effects*
  • Lymphocyte Culture Test, Mixed
  • Mice
  • Peptidylprolyl Isomerase
  • Structure-Activity Relationship
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Carrier Proteins
  • Cyclosporins
  • Ethers
  • Immunosuppressive Agents
  • Interleukin-2
  • Ionomycin
  • Peptidylprolyl Isomerase
  • Tetradecanoylphorbol Acetate