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.
Hu
Weimin
W
Department of Applied Biological Science, Tokyo Noko University, 3-5-8 Saiwaicho, Fuchu, Tokyo 183-8509, Japan.
Kitano
Yoshikazu
Y
Hasumi
Keiji
K
D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D010960:Plasminogen Activators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D001578:Benzopyrans; D011760:Pyrrolidinones; D010960:Plasminogen Activators