Longestin
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| Category | Enzyme inhibitors |
| Catalog number | BBF-03610 |
| CAS | 131774-53-3 |
| Molecular Weight | 1093.34 |
| Molecular Formula | C61H88O17 |
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Description
It is produced by the strain of Streptomyces argenteolus A-2. Longestin inhibited Ca2+ and CAM-PDE in bovine brain with an IC50 of 0.065 μmol/L.
Specification
| Synonyms | KS-505a; 2-((6-carboxy-4,5-dihydroxy-3-methoxytetrahydro-2H-pyran-2-yl)oxy)-14-hydroxy-8a,10a-bis(hydroxymethyl)-14-(3-methoxy-3-oxopropyl)-1,4,4a,6,6a,17b,19b,21b-octamethyl-16-oxo-2,3,4,4a,4b,5,6,6a,6b,7,8,8a,8b,9,10,10a,14,16,17,17a,17b,18,19,19a,19b,20,21,21a,21b,22,23,23a-dotriacontahydro-1H-benzo[9,10]piceno[3,4-a]furo[3,4-j]xanthene-1-carboxylic acid |
| IUPAC Name | 11-(6-carboxy-4,5-dihydroxy-3-methoxyoxan-2-yl)oxy-32-hydroxy-22,26-bis(hydroxymethyl)-32-(3-methoxy-3-oxopropyl)-2,6,10,13,14,17,18,39-octamethyl-34-oxo-27,33-dioxadecacyclo[20.19.0.02,19.05,18.06,15.09,14.023,39.026,38.028,36.031,35]hentetraconta-28(36),29,31(35)-triene-10-carboxylic acid |
| Canonical SMILES | CC1CC2C(CCC3C2(C(CC(C3(C)C(=O)O)OC4C(C(C(C(O4)C(=O)O)O)O)OC)C)C)(C5C1(C6CCC7(C(C6(CC5)C)CCC8(C7CCC9(C8CC1=C(O9)C=CC2=C1C(=O)OC2(CCC(=O)OC)O)CO)C)CO)C)C |
| InChI | InChI=1S/C61H88O17/c1-30-25-40-54(4,21-15-39-57(40,7)31(2)26-42(58(39,8)52(70)71)75-51-48(74-10)46(66)45(65)47(76-51)49(67)68)35-13-19-53(3)36(56(30,35)6)16-22-59(28-62)37(53)14-20-55(5)38(59)17-23-60(29-63)41(55)27-32-34(77-60)12-11-33-44(32)50(69)78-61(33,72)24-18-43(64)73-9/h11-12,30-31,35-42,45-48,51,62-63,65-66,72H,13-29H2,1-10H3,(H,67,68)(H,70,71) |
| InChI Key | DBIAGVXGCNWASW-UHFFFAOYSA-N |
Properties
| Appearance | Yellow Powder |
| Density | 1.36 g/cm3 |
| Solubility | Soluble in Methanol, DMSO, Ethyl acetate |
Reference Reading
1. Enzymatic Formation of a Skipped Methyl-Substituted Octaprenyl Side Chain of Longestin (KS-505a): Involvement of Homo-IPP as a Common Extender Unit
Taro Ozaki, Sandip S Shinde, Lei Gao, Ryo Okuizumi, Chengwei Liu, Yasushi Ogasawara, Xiaoguang Lei, Tohru Dairi, Atsushi Minami, Hideaki Oikawa Angew Chem Int Ed Engl. 2018 May 28;57(22):6629-6632. doi: 10.1002/anie.201802116. Epub 2018 Apr 26.
Longestin (KS-505a), a specific inhibitor of phosphodiesterase, is a meroterpenoid that consists of a unique octacyclic terpene skeleton with branched methyl groups at unusual positions (C1 and C12). Biochemical analysis of Lon23, a methyltransferase involved in the biosynthesis of longestin, demonstrated that it methylates homoisopentenyl diphosphate (homo-IPP) to afford (3Z)-3-methyl IPP. This compound, along with IPP, is selectively accepted as extender units by Lon22, a geranylgeranyl diphosphate (GGPP) synthase homologue, to yield dimethylated GGPP (dmGGPP). The absolute configuration of dmGGPP was determined to be (4R,12R) by degradation and chiral GC analysis. These findings allowed us to propose an enzymatic sequence for key steps of the biosynthetic pathway of the unusual homoterpenoid longestin.
2. In vitro and in vivo antitrypanosomal activitiy of two microbial metabolites, KS-505a and alazopeptin
Aki Ishiyama, Kazuhiko Otoguro, Miyuki Namatame, Aki Nishihara, Toshiaki Furusawa, Rokuro Masuma, Kazuro Shiomi, Yoko Takahashi, Michio Ichimura, Haruki Yamada, Satoshi Omura J Antibiot (Tokyo). 2008 Oct;61(10):627-32. doi: 10.1038/ja.2008.83.
Our on-going screening program to discover new antitrypanosomal antibiotics has been evaluating compounds isolated from soil microorganisms as well as investigating the antibiotic libraries of the Kitasato Institute for Life Sciences and BioFrontier Laboratories of Kyowa Hakko Kogyo Co., Ltd. We have now discovered two compounds, KS-505a and alazopeptin, which exhibit moderate antitrypanosomal characteristics. We report here the in vitro and in vivo antitrypanosomal activities and cytotoxicities of KS-505a and alazopeptin, compared with some commonly-used antitrypanosomal drugs. This is the first report of in vitro and in vivo antitrypanosomal activities of either KS-505a or alazopeptin.
3. Cloning of the gene cluster responsible for biosynthesis of KS-505a (longestin), a unique tetraterpenoid
Yutaka Hayashi, Hiroyasu Onaka, Nobuya Itoh, Haruo Seto, Tohru Dairi Biosci Biotechnol Biochem. 2007 Dec;71(12):3072-81. doi: 10.1271/bbb.70477. Epub 2007 Dec 7.
KS-505a (longestin), produced by Streptomyces argenteolus, has a unique structure that consists of a tetraterpene (C40) skeleton, to which a 2-O-methylglucuronic acid and an o-succinyl benzoate moiety are attached. It is a novel inhibitor of calmodulin-dependent cyclic-nucleotide phosphodiesterase, which is representative of a potent anti-amnesia drug. As a first step to understanding the biosynthetic machinery of this unique and pharmaceutically useful compound, we cloned a KS505a biosynthetic gene cluster. First we searched for a gene encoding octaprenyl diphosphates, which yielded a C40 precursor by PCR, and four candidate genes were obtained. Among these, one was confirmed to have the expected enzyme activity by recombinant enzyme assay. On the basis of an analysis of the flanking regions of the gene, a putative KS-505a biosynthetic gene cluster consisting of 24 ORFs was judged perhaps to be present on a 28-kb DNA fragment. A gene disruption experiment was also employed to confirm that the cluster indeed participated in KS-505a biosynthesis. This is believed to be the first report detailing the gene cluster of a cyclized tetraterpenoid.
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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 ╳
