Abstract
Cyclosporin A (ciclosporin), a potent and clinically important immunosuppressive drug (Sandimmun), represents the main component of a group of over 25 closely related, cyclic undecapeptides produced by the fungus Tolypocladium inflatum. By feeding experiments using DL-α-allylglycine as precursor, specific incorporation in position 2 was attained leading to [Allylgly2]cyclosporin A. Exogenously supplied L-β-cyclohexylalanine results in the almost exclusive production of [MeCyclohexylala1]cyclosporin A (replacement of methylbutenylmethylthreonine-1). D-Alanine in position 8 can be successfully substituted by D-serine. The new [D-Ser8] analogues of the cyclosporins A, C, D and G as well as [Allylgly2]cyclosporin A exhibit high immunosuppressive effects.
