MMPACE- A novel screening assay for MMP inhibitors
A wide range of human diseases such as diabetes mellitus typ I and autoimmune diseases like rheumatoid arthritis (RA) or multiple sclerosis (MS) go along with malfunctions in the regulation of matrix metalloproteinases, especially MMP-2 and MMP-9. The development and validation of novel inhibitors for MMP´s is often hampered by high costs of MMP production and purification from human tumor cells or fibroblasts and the necessity for subsequent in vitro activation steps by per se toxic anorganic compounds.
An innovative cell based MMP bioassay was invented, enabling high through-put screening of novel MMP inhibitors. The method is based on the heterologous expression and immobilization of biologically active forms of human MMP-2 and MMP-9 on the cell surface of the yeast Pichia pastoris via a novel, highly efficient cell surface display system. Yeast cells modified in this way can either be provided as fresh cells or freeze-dried, enabling their direct use in MMP inhibitor screenings.
- Easy production with a GRAS status microorganism;
- Less expensive production of the MMPace cells by fed-batch fermentation in a bioreactor;
- No cost intensive purification procedures;
- No environmentally harmful activation steps;
- As easy to use as dissolved enzymes.
- Bioassay for high through-put screening of novel MMP inhibitors.