Synthesis of 5-Fluoroproline Derivatives,

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.

Document Details

Document Type
Technical Report
Publication Date
Jan 01, 1992
Accession Number
ADP008548

Entities

People

  • Daniel H. Rich
  • James L. Kofron
  • John R. Kagel

Organizations

  • University of Wisconsin–Madison

Tags

DTIC Thesaurus Topics

  • Biochemistry
  • Carrier Proteins
  • Chemical Compounds
  • Chemical Synthesis
  • Chemistry
  • Electrons
  • Enzymes
  • Inhibitors
  • Isomerases
  • Isomerization
  • Massachusetts
  • Nitrogen
  • Proteins
  • Substrates

Fields of Study

  • Chemistry

Readers

  • Cellular and Molecular Pathways of Apoptosis.
  • Molecular and Cellular Biochemistry
  • Organic Chemistry

Technology Areas

  • Microelectronics