THERAPEUTIC ANTI-METASTATIC ENZYME

PUBLISHED DATA SUGGESTS THAT REDUCED SERUM TYROSINE AND PHENYLALANINE CONCENTRATIONS REDUCE THE NUMBER OF METASTASIS IN VARIOUS ANIMAL CANCER MODELS AS WELL AS HUMAN PATIENTS. THE LONGTERM GOAL OF THIS WORK IS TO CLONE, EXPRESS AND EVALUATE THERAPEUTIC ENZYMES THAT CATABOLIZE ONE OR BOTH OF THESE AMINO ACIDS. FOR THIS PRELIMINARY WORK A THERPAEUTIC ENZYME [L-TYROSINE DECARBOXYLASE[TYRDC](EC4.1.1.25)] PURIFIED FORM ERWINIA HERBICOLA PREVIOUSLY SHOWN TO ATTENUATE MELANOMA GROWTH IN VIVO HAS BEEN SELECTED. TYRDC WILL BE PURIFIED USING A NEW SENSITIVE ASSAY AND THE AMINO ACID SEQUENCE WILL BE DETERMINED. THIS SEQUENCE WILL BE USED TO DESIGN OLIGONUCLEOTIDE PROBES/PRIMERS. THESE REAGENTS WILL BE USED TO SCREEN A GENOMIC LIBRARY CONSTRUCTED FROM ERWINIA HERBICOLA. EXPRESSION AND PURIFICATION OF THE RECOMBINANT TYRDC IN PHASE 2 WILL PROVIDE A VALUABLE REAGENT TO INVESTIGATE IN ANIMAL MODELS OF TUMOR GROWTH AND METASTASIS. IF THESE STUDIES DEMONSTRATE A BENEFICIAL EFFECT PRECLINICAL DEVELOPMENT OF THIS NOVEL ENZYME IS INDICATED.