环孢霉素
Contents
Brief introduction Fermentatrification and analysis.
Pharmacokinetics and toxicity
Therapeutic uses
Brief introduction
3.Biosynthesis
A
possible mechanism of CyA synthesis:
• Synthesis of all 11 constituent amino acids • Activation of each amino acid • N-methylation and peptide bond formation, and finally • The cyclization reaction
1.History
In 1973, CyA was purified from the fungal extract of T. inflatum. in 1975 ,complete structural analysis was established. in 1983 ,CyA was approved by the USFDA for clinical use to prevent. graft rejection in transplantation. In 1984, synthetic CyA was produced.
Effect of carbon source:Carbon source to not only affect the magnitude of CyA production, but also the proportion of individual components of the cyclosporin mixture. The best specific production of cyclosporins was achieved using glucose.
Fermentative production
1.Fermentation parameters
Microorganisms: T. inflatum has emerged as the most widely used. carbon
sources：glucose，maltose，starch ，fructose，sorbose.
Immunosuppressants are a class of drugs which are capable of inhibiting the body's immune system . T h e s e drugs are used in organ transplant patients to prevent rejection of the organ by the body by decreasing the body's own natural defense to foreign bodies, and are also useful in the treatment of autoimmune diseases.CyA is one of the most commonly prescribed immunosuppressive drugs for the treatment of patients with organ transplantation and autoimmune diseases including AIDS owing to its superior T-cell specificity and low levels of myelotoxicity.
2.Chemical structure and Physical properties I t is made up of eleven amino acids, ten of which are known aliphatic amino acids but the amino acid at position one was unknown. molecular weight:1202.6 melting point: (natural) and 149 °C -150 °C (synthetic) solubility : s l i g h t l y soluble in water and soluble in organic solvents is easy. 148 - 151 °C

I t was initially believed that CyA mediates its immunosuppressive effects by blocking the PPI activity of the cyclophilin. Some of the immunosuppressive effects of CyA have also been attributed to the ability to induce the production of the potent immunosuppressive cytokine TGF- β.
E
xogenous supply of amino acid precursors in the fermentation medium to strongly influence the cyclosporin biosynthesis.
4.Mode of action Immunosuppressants affect various components of the immune system such as T-helper, T-effector cell function, antigen presentation and B-lymphocyte cell function.