Accession Number : ADP008548

Title :   Synthesis of 5-Fluoroproline Derivatives,

Corporate Author : WISCONSIN UNIV-MADISON

Personal Author(s) : Kagel, John R. ; Kofron, James L. ; Rich, Daniel H.

Report Date : 1992

Pagination or Media Count : 2

Abstract : Cyclophilin, a major cytosolic binding protein, is the first peptidyl-prolyl cis-trans isomerase (PPIase) identified. this enzyme catalyzes cis-trans isomerization of X-Pro bonds, an isomerization that may be a rate limiting step in some protein-folding reactions, and that may correlate with the immunosuppressive activity of the drug, Cyclosporin-A. Fluoroproline (5-FPro, 1), which has not been reported previously, is expected to be unstable due to the potential for imine formulation. Hypothesizing that acyl derivatives of 5-FPro might be sufficiently stable to be assayed as inhibitors of PPIase, due to the delocalization of the lone pair of electrons on nitrogen into the adjacent carbonyl group, we have synthesized a series of 5-FPro-containing substrates.

Descriptors :   *ISOMERASES, *IMMUNOSUPPRESSION, ISOMERIZATION, SYNTHESIS(CHEMISTRY), AMINO ACIDS, FLUORINE COMPOUNDS.

Subject Categories : Biochemistry
      Pharmacology

Distribution Statement : APPROVED FOR PUBLIC RELEASE