Sparsomycin
(Synonyms: 司帕索霉素) 目录号 : GC46223A bacterial metabolite with diverse biological activities
Cas No.:1404-64-4
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Sparsomycin is a bacterial metabolite and a nucleoside analog of uracil that has been found in S. sparsogenes and has diverse biological activities.1,2,3 It is active against KB carcinoma cells, Gram-positive and Gram-negative bacteria, and fungi.4 Sparsomycin is an inhibitor of peptidyl transferase that interferes with tRNA binding to the A-site of the peptidyl transfer center and increases the binding of peptidyl-tRNA to the P-site.2 It inhibits protein synthesis in bacteria, archaea, and eukaryotes.2,3 Sparsomycin reduces tumor growth in a P388 mouse leukemia model and in a Walker 256 carcinosarcoma rat model.5
|1. Ottenheijm, H.C., van den Broek, L.A., Ballesta, J.P., et al. Chemical and biological aspects of sparsomycin, an antibiotic from Streptomyces. Prog. Med. Chem. 23, 219-268 (1986).|2. Wilson, D.N. The A-Z of bacterial translation inhibitors. Crit. Rev. Biochem. Mol. Biol. 44(6), 393-433 (2009).|3. Lazaro, E., Van den Broek, L.A., San Felix, A., et al. Chemical, biochemical and genetic endeavours characterizing the interaction of sparsomycin with the ribosome. Biochimie 73(7-8), 1137-1143 (1991).|4. Owen, S.P., Dietz, A., and Camiener, G.W. Sparsomycin, a new antitumor antibiotic. I. Discovery and biological properties. Antimicrob. Agents Chemother. 1962, 772-779 (1963).|5. Zylicz, Z., Wagener, D.J., van Rennes, H., et al. In vivo antitumor activity of sparsomycin and its analogues in eight murine tumor models. Invest. New Drugs 6(4), 285-292 (1988).
| Cas No. | 1404-64-4 | SDF | |
| 别名 | 司帕索霉素 | ||
| Canonical SMILES | O=C1C(/C=C/C(N[C@@H](CO)C[S@](CSC)=O)=O)=C(C)NC(N1)=O | ||
| 分子式 | C13H19N3O5S2 | 分子量 | 361.4 |
| 溶解度 | H2O : 1 mg/mL (2.77 mM; Need ultrasonic and warming) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.767 mL | 13.8351 mL | 27.6702 mL |
| 5 mM | 0.5534 mL | 2.767 mL | 5.534 mL |
| 10 mM | 0.2767 mL | 1.3835 mL | 2.767 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Sparsomycin Exhibits Potent Antiplasmodial Activity In Vitro and In Vivo
Pharmaceutics 2022 Feb 28;14(3):544.PMID:35335918DOI:10.3390/pharmaceutics14030544.
The emerging spread of drug-resistant malaria parasites highlights the need for new antimalarial agents. This study evaluated the growth-inhibitory effects of Sparsomycin (Sm), a peptidyl transferase inhibitor, against Plasmodium falciparum 3D7 (chloroquine-sensitive strain), P. falciparum K1 (resistant to multiple drugs, including chloroquine), P. yoelii 17XNL (cause of uncomplicated rodent malaria) and P. berghei ANKA (cause of complicated rodent malaria). Using a fluorescence-based assay, we found that Sm exhibited half-maximal inhibitory concentrations (IC50) of 12.07 and 25.43 nM against P. falciparum 3D7 and K1, respectively. In vitro treatment of P. falciparum 3D7 with Sm at 10 or 50 nM induced morphological alteration, blocked parasites in the ring state and prevented erythrocyte reinvasion, even after removal of the compound. In mice infected with P. yoelii 17XNL, the administration of 100 μg/kg Sm for 7 days did not affect parasitemia. Meanwhile, treatment with 300 μg/kg Sm resulted in a significantly lower parasitemia peak (18.85%) than that observed in the control group (40.13%). In mice infected with P. berghei ANKA, both four and seven doses of Sm (300 μg/kg) prolonged survival by 33.33%. Our results indicate that Sm has potential antiplasmodial activities in vitro and in vivo, warranting its further development as an alternative treatment for malaria.
Sparsomycin and its analogues: a new approach for evaluating their potency as inhibitors of peptide bond formation
Mol Pharmacol 1996 Jun;49(6):1085-91.PMID:8649347doi
The ability of several Sparsomycin analogues to inhibit peptide bond formation was studied in vitro. Peptide bonds are formed between puromycin (S) and the acetylPhe-tRNA of acetylPhe-tRNA/70 S ribosome/poly(U) complex (complex C), according to the puromycin reaction: [formula: see text] It was shown that the Sparsomycin analogues, like Sparsomycin itself, inhibit peptide bond formation in a time-dependent manner; they react with complex C according to the equation [formula: see text] where C*I is a conformationally altered species in which I is bound more tightly than in CI. The determination of the rate constant k(7) for the regeneration of complex C from the C*I complex allows evaluation of these analogues as inhibitors of peptide bond formation. According to their k7 values, these analogues are classified in order of descending potency as follows: n-pentyl-sparsomycin (4) > n-butyl-sparsomycin (3) approximately n-butyl-deshydroxy-sparsomycin (6) > benzyl-sparsomycin (2) > deshydroxy-sparsomycin (5) approximately Sparsomycin (1) > n-propyl-desthio-deshydroxy-sparsomycin (7). The analogues with an aromatic or a larger hydrophobic side chain are stronger inhibitors of the puromycin reaction than are those with a smaller side chain or those lacking the bivalent sulfur atoms; replacement of the hydroxymethyl group with a methyl group does not affect the position of the compound in this ranking; compare the positions of compounds 1 and 3 with those of 5 and 6. In the case of compound 7, C*I adsorbed on cellulose nitrate disks was not sufficiently stable to allow examination by the method applied to the other analogues, probably due to a relatively large value of k7. This analogue showed also time-dependent inhibition, but after the isomerization of CI to C*I, the kinetics of inhibition become complex, and C*I interacted further with puromycin, either as C*I or after its dissociation to C*.
Sparsomycin Biosynthesis Highlights Unusual Module Architecture and Processing Mechanism in Non-ribosomal Peptide Synthetase
ACS Chem Biol 2015 Aug 21;10(8):1765-9.PMID:26046698DOI:10.1021/acschembio.5b00284.
Sparsomycin is a model protein synthesis inhibitor that blocks peptide bond formation by binding to the large ribosome subunit. It is a unique dipeptidyl alcohol, consisting of a uracil acrylic acid moiety and a monooxo-dithioacetal group. To elucidate the biosynthetic logic of Sparsomycin, a biosynthetic gene cluster for Sparsomycin was identified from the producer Streptomyces sparsogenes by genome mining, targeted gene mutations, and heterologous expression. Both the genetic and enzymatic studies revealed a minimum set of non-ribosomal peptide synthetases needed for generating the dipeptidyl alcohol scaffold of Sparsomycin, featuring unusual mechanisms in dipeptidyl assembly and off-loading.
Chemical, biochemical and genetic endeavours characterizing the interaction of Sparsomycin with the ribosome
Biochimie 1991 Jul-Aug;73(7-8):1137-43.PMID:1720666DOI:10.1016/0300-9084(91)90157-v.
Sparsomycin interaction with the ribosome and characteristics of the drug binding site in the particle were studied using chemical modification of the drug, affinity labeling methods and isolation of drug resistant mutants. The structure-function relationship studies, performed with a large number of drug derivatives, indicate that the drug interacts with the ribosome by its western and eastern moieties. The uracil ring, in the western end of the drug molecule, probably forms hydrogen bonds with the rRNA, while the apolar CH3-S-CH3 group in the eastern end interacts with a hydrophobic ribosomal domain that affinity labeling results seem to indicate is formed by protein. An increase in lipophilicity in this part of the antibiotic results in a dramatic increase in the inhibitory activity of the drug. The Sparsomycin binding site is not accessible in free ribosomes, but the presence of an N-blocked amino acyl-tRNA at the P-site turns the particles capable of reversible interaction with the drug. After failure using Escherichia coli, a sparsomycin-resistant mutant was obtained by direct mutagenesis on Halobacterium halobium, a species with a unique copy of rRNA genes, stressing the role of rRNA on the drug interaction site.
Sparsomycin-linezolid conjugates can promote ribosomal translocation
Chembiochem 2011 Dec 16;12(18):2801-6.PMID:22038852DOI:10.1002/cbic.201100508.
Sparsomycin is an antibiotic that targets the peptidyl transferase center of the ribosome and has the ability to promote ribosomal translocation in the absence of EF-G and GTP. Here we show that changes in the configurations at the two chiral centers of Sparsomycin, especially at the chiral carbon, can greatly affect its capability to promote ribosomal translocation. More importantly, the incorporation of the pseudo-uracil moiety of Sparsomycin into linezolid through a covalent linkage conferred on linezolid derivatives the ability to promote translocation, thus indicating the importance of interactions between this pseudo-uracil moiety, rRNA, and tRNA for promoting translocation. In addition, these translocation promoters can also effectively inhibit spontaneous reverse translocation; this suggests that they might promote forward translocation by trapping the ribosome in the post-translocation state and shifting the equilibrium between the pre- and post-translocation ribosome in the forward direction.