SMTP-6
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| Category | Bioactive by-products |
| Catalog number | BBF-02470 |
| CAS | |
| Molecular Weight | 572.7 |
| Molecular Formula | C34H40N2O6 |
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Description
SMTP-6 is a Staplabin homolog isolated from Stachybotrys microspora IFO30018. It enhanced the binding of Plasminogen to Fibrin.
Specification
| IUPAC Name | 2-[2-[(3E)-4,8-dimethylnona-3,7-dienyl]-3,5-dihydroxy-2-methyl-7-oxo-4,9-dihydro-3H-pyrano[2,3-e]isoindol-8-yl]-3-(1H-indol-3-yl)propanoic acid |
| Canonical SMILES | CC(=CCCC(=CCCC1(C(CC2=C(C=C3C(=C2O1)CN(C3=O)C(CC4=CNC5=CC=CC=C54)C(=O)O)O)O)C)C)C |
| InChI | InChI=1S/C34H40N2O6/c1-20(2)9-7-10-21(3)11-8-14-34(4)30(38)17-25-29(37)16-24-26(31(25)42-34)19-36(32(24)39)28(33(40)41)15-22-18-35-27-13-6-5-12-23(22)27/h5-6,9,11-13,16,18,28,30,35,37-38H,7-8,10,14-15,17,19H2,1-4H3,(H,40,41)/b21-11+ |
| InChI Key | CJZYCBIYGYFBTP-SRZZPIQSSA-N |
Reference Reading
1. Nonlysine-analog plasminogen modulators promote autoproteolytic generation of plasmin(ogen) fragments with angiostatin-like activity
Shigeki Ohyama, Tomotaka Harada, Toshihiro Chikanishi, Yutaka Miura, Keiji Hasumi Eur J Biochem. 2004 Feb;271(4):809-20. doi: 10.1111/j.1432-1033.2004.03985.x.
We recently discovered several nonlysine-analog conformational modulators for plasminogen. These include SMTP-6, thioplabin B and complestatin that are low molecular mass compounds of microbial origin. Unlike lysine-analog modulators, which increase plasminogen activation but inhibit its binding to fibrin, the nonlysine-analog modulators enhance both activation and fibrin binding of plasminogen. Here we show that some nonlysine-analog modulators promote autoproteolytic generation of plasmin(ogen) derivatives with its catalytic domain undergoing extensive fragmentation (PMDs), which have angiostatin-like anti-endothelial activity. The enhancement of urokinase-catalyzed plasminogen activation by SMTP-6 was followed by rapid inactivation of plasmin due to its degradation mainly in the catalytic domain, yielding PMD with a molecular mass ranging from 68 to 77 kDa. PMD generation was observed when plasmin alone was treated with SMTP-6 and was inhibited by the plasmin inhibitor aprotinin, indicating an autoproteolytic mechanism in PMD generation. Thioplabin B and complestatin, two other nonlysine-analog modulators, were also active in producing similar PMDs, whereas the lysine analog 6-aminohexanoic acid was inactive while it enhanced plasminogen activation. Peptide sequencing and mass spectrometric analyses suggested that plasmin fragmentation was due to cleavage at Lys615-Val616, Lys651-Leu652, Lys661-Val662, Lys698-Glu699, Lys708-Val709 and several other sites mostly in the catalytic domain. PMD was inhibitory to proliferation, migration and tube formation of endothelial cells at concentrations of 0.3-10 microg.mL(-1). These results suggest a possible application of nonlysine-analog modulators in the treatment of cancer through the enhancement of endogenous plasmin(ogen) fragment formation.
2. Structure-activity relationships of 11 new congeners of the SMTP plasminogen modulator
Keiko Hasegawa, Haruki Koide, Weimin Hu, Naoko Nishimura, Ritsuko Narasaki, Yoshikazu Kitano, Keiji Hasumi J Antibiot (Tokyo). 2010 Oct;63(10):589-93. doi: 10.1038/ja.2010.101. Epub 2010 Sep 15.
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.
3. Evaluation of the effects of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model
Keita Shibata, Terumasa Hashimoto, Keiji Hasumi, Kazuo Honda, Koji Nobe Eur J Pharmacol. 2018 Jan 5;818:221-227. doi: 10.1016/j.ejphar.2017.10.055. Epub 2017 Oct 28.
We reported previously that Stachybotrys microspora triprenyl phenol-7 (SMTP-7) showed potential thrombolytic, anti-inflammatory and anti-oxidant effects that account for its excellent pharmacological activity such as having a wider therapeutic time window than tissue plasminogen activator (t-PA) and a significant protection against hemorrhage. The aim of the present study was to evaluate and compare the effect of a new series of SMTPs in the acetic acid-induced embolic cerebral infarct mouse model. Thrombotic occlusion was produced in mice by inducing the transfer of acetic acid-induced thrombi from the right common carotid artery into the brain. SMTPs were evaluated by their effect on reducing infarct area, neurological score and edema. Furthermore, plasmin formation, anti-inflammatory and anti-oxidant activities were assessed by fibrin zymography, measuring pro-inflammatory gene expression, and thiobarbituric acid reactive substances (TBARS) assay, respectively. Treatment with either SMTP-22 or SMTP-43 (10mg/kg), which have similar plasmin formation, anti-inflammatory and anti-oxidant activities to SMTP-7, resulted in reduced infarct area, neurological score and edema. Coexistence of all these three activities appears to be important for the treatment of embolic infarction because SMTP-6, SMTP-25, and SMTP-44D (10mg/kg), which are each missing at least one of the three functions, were not as effective. Therefore, these results indicate that SMTP-22 and SMTP-43 have potential as medicinal compounds for the treatment of embolic cerebral infarction.
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Bio Calculators
* Our calculator is based on the following equation:
Concentration (start) x Volume (start) = Concentration (final) x Volume (final)
It is commonly abbreviated as: C1V1 = C2V2
* Total Molecular Weight:
g/mol
Tip: Chemical formula is case sensitive. C22H30N4O √ c22h30n40 ╳
