Belactosin C
* Please be kindly noted products are not for therapeutic use. We do not sell to patients.
| Category | Antibiotics |
| Catalog number | BBF-00276 |
| CAS | 189871-55-4 |
| Molecular Weight | 357.40 |
| Molecular Formula | C16H27N3O6 |
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Description
Belactosin C is produced by the strain of Streptomyces sp. No antibacterial activity. C inhibits the IC50 of HeLa S3 cells is 200μmol/L.
Specification
| Synonyms | SCHEMBL3448978; CHEMBL1783833 |
| IUPAC Name | (2S)-2-[[(2S)-2-aminopropanoyl]amino]-5-[[(2R,3S)-3-[(2S)-butan-2-yl]-4-oxooxetane-2-carbonyl]amino]pentanoic acid |
| Canonical SMILES | CCC(C)C1C(OC1=O)C(=O)NCCCC(C(=O)O)NC(=O)C(C)N |
| InChI | InChI=1S/C16H27N3O6/c1-4-8(2)11-12(25-16(11)24)14(21)18-7-5-6-10(15(22)23)19-13(20)9(3)17/h8-12H,4-7,17H2,1-3H3,(H,18,21)(H,19,20)(H,22,23)/t8-,9-,10-,11-,12+/m0/s1 |
| InChI Key | ZFCGPWGFGUDLHO-UHFZAUJKSA-N |
Properties
| Appearance | White Powder |
| Antibiotic Activity Spectrum | neoplastics (Tumor) |
| Melting Point | 212-215 °C |
Reference Reading
1. Synthesis and biological activity of simplified belactosin C analogues
Armin de Meijere, Vadim S Korotkov, Alexander V Lygin, Oleg V Larionov, Viktor V Sokolov, Tine Graef, Mazen Es-Sayed Org Biomol Chem. 2012 Aug 21;10(31):6363-74. doi: 10.1039/c2ob25586c. Epub 2012 Jun 26.
Successful biochemical studies of the natural products belactosin A and C and their acylated congeners have shown a β-lactonecarboxamide moiety to be a possible core structure of powerful proteasome inhibitors. As a part of further investigations, variously decorated simplified β-lactonecarboxamides have been synthesized in order to understand structure-biological activity relations in detail, to find ways of improving their biological activity and stability and to reduce the complexity of their preparation. Biological tests showed that the best compounds possess a high potential against phytopathogenic fungi in the greenhouse.
2. Biosynthesis of the β-Lactone Proteasome Inhibitors Belactosin and Cystargolide
Felix Wolf, Judith S Bauer, Theresa M Bendel, Andreas Kulik, Jörn Kalinowski, Harald Gross, Leonard Kaysser Angew Chem Int Ed Engl. 2017 Jun 1;56(23):6665-6668. doi: 10.1002/anie.201612076. Epub 2017 Apr 28.
Belactosins and cystargolides are natural product proteasome inhibitors from Actinobacteria. Both feature dipeptidic backbones and a unique β-lactone building block. Herein, we present a detailed investigation of their biosynthesis. Identification and analysis of the corresponding gene clusters indicated that both compounds are assembled by rare single-enzyme amino acid ligases. Feeding experiments with isotope-labeled precursors and in vitro biochemistry showed that the formation of the β-lactone warhead is unprecedented and reminiscent of leucine biosynthesis, and that it involves the action of isopropylmalate synthase homologues.
3. A strategy for dual inhibition of the proteasome and fatty acid synthase with belactosin C-orlistat hybrids
Mingzhao Zhu, Wayne D Harshbarger, Omar Robles, et al. Bioorg Med Chem. 2017 Jun 1;25(11):2901-2916. doi: 10.1016/j.bmc.2017.01.020. Epub 2017 Jan 19.
The proteasome, a validated cellular target for cancer, is central for maintaining cellular homeostasis, while fatty acid synthase (FAS), a novel target for numerous cancers, is responsible for palmitic acid biosynthesis. Perturbation of either enzymatic machine results in decreased proliferation and ultimately cellular apoptosis. Based on structural similarities, we hypothesized that hybrid molecules of belactosin C, a known proteasome inhibitor, and orlistat, a known inhibitor of the thioesterase domain of FAS, could inhibit both enzymes. Herein, we describe proof-of-principle studies leading to the design, synthesis and enzymatic activity of several novel, β-lactone-based, dual inhibitors of these two enzymes. Validation of dual enzyme targeting through activity-based proteome profiling with an alkyne probe modeled after the most potent inhibitor, and preliminary serum stability studies of selected derivatives are also described. These results provide proof of concept for dual targeting of the proteasome and fatty acid synthase-thioesterase (FAS-TE) enabling a new approach for the development of drug-candidates with potential to overcome resistance.
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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 ╳
