SMTP-4D, -5D, -6D, -7D and -8D, a new series of the non-lysine-analog plasminogen modulators with a D-amino acid moiety.

Staplabin and SMTPs, triprenyl phenol metabolites of the fungus Stachybotrys microspora, are a family of non-lysine-analog plasminogen modulators that enhance both activation and fibrin binding of plasminogen by modulating plasminogen conformation. These compounds, including SMTP-4, -5, -6, -7 and -8, have an amino acid or an amino alcohol moiety in their structure, and precursor amine feeding greatly increases the biosynthesis of a metabolite of interest. In the present study, we have isolated five novel SMTPs (designated SMTP-4D, -5D, -6D, -7D and -8D) from precursor D-amino acid-fed cultures. Physico-chemical properties as well as chromatographic behavior were distinct from those of the corresponding L-amino acid analogs, which are selectively accumulated in L-amino acid-fed cultures and share common properties with corresponding natural products. The D-series SMTPs enhanced urokinase-catalyzed plasminogen activation by 10-fold at 80 approximately 180 microM.