title: Structure-activity relationships of 11 new congeners of the SMTP plasminogen modulator.
abstract: The fungal metabolite Stachybotrys microspora triprenyl phenols (SMTPs) are small-molecule plasminogen modulators that enhance plasminogen activation. The SMTP molecule consists of a tricyclic γ-lactam moiety, an isoprene side-chain and an N-linked side-chain. Previous investigations have demonstrated that the N-linked side-chain is crucial for its activity. In this study, we have isolated 11 new SMTP congeners with a variety of N-linked side-chain structures, to investigate structure-activity relationships. Active compounds included congeners with a carboxyl or a sulfonic acid group in the N-linked side-chain, whereas not all the congeners with a carboxyl group were active. Of these congeners, that with methionine or tyrosine as the N-linked side-chain moiety was more active than that with an aliphatic amino acid. Congeners without ionizable group in the N-linked side-chain were essentially inactive.
authors.affiliation: Department of Applied Biological Science, Tokyo Noko University, Tokyo, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Hasegawa
authors.forename: Haruki
authors.initials: H
authors.lastname: Koide
authors.forename: Weimin
authors.initials: W
authors.lastname: Hu
authors.forename: Naoko
authors.initials: N
authors.lastname: Nishimura
authors.forename: Ritsuko
authors.initials: R
authors.lastname: Narasaki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Kitano
authors.forename: Keiji
authors.initials: K
authors.lastname: Hasumi
mesh_terms: D001578:Benzopyrans / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D010960:Plasminogen Activators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011760:Pyrrolidinones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D013191:Stachybotrys / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D001578:Benzopyrans; D011760:Pyrrolidinones; C117808:SMTP 4; C117810:SMTP 6; D010960:Plasminogen Activators