Decoyinine (Angustmycin A)
(Synonyms: 德夸菌素) 目录号 : GC33093
A nucleoside analog and GMP synthase inhibitor
Cas No.:2004-04-8
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Cell experiment: | The isogenic strains WLN-4 (sacA321 amyRJ-amyE+) and WLN-11 (sacA321 gra-10-amyE+) are inoculated into minimal S7 medium, containing 2% (wt/vol) glucose, from washed exponential-phase seed cultures grown in the same medium. At mid-logarithmic growth phase, each culture is evenly subdivided into two flasks containing either 1/10 the culture volume of fresh S7 medium or a 1/10 volume of filter-sterilized S7 medium to which 2.5 mg of Decoyinine per ml has previously been dissolved (final Decoyinine concentration, 250 μg/mL). At regular intervals before and after the decoyinine addition, samples are removed from the cultures and the culture supernatants are assayed for a-amylase as described previously. At 16 h after the Decoyinine addition, the frequency of heatresistant spores in each culture is determined[2]. |
Animal experiment: | Mice[1]SK-Mel-103 and SK-Mel-28 cells are inoculated subcutaneously in both flanks of SCID mice (18 mice/cell line). Once tumors volume reach approximately 100 mm3, mice are randomly assigned to one of four groups and treated with daily i.p. injections of Decoyinine (120 mg/kg), MMF (30 mg/kg), or with respective vehicles. Tumor size is measured every other day with a caliper and mice are killed once tumor volume reach 1000 mm3 or the animals show signs of morbidity[1]. |
References: [1]. A Bianchi-Smiraglia, et al. Pharmacological targeting of guanosine monophosphate synthase suppresses melanoma cell invasion and tumorigenicity. Cell Death Differ. 2015 Nov; 22(11): 1858–1864. | |
Decoyinine is a nucleoside analog and a reversible and non-competitive inhibitor of GMP synthase (IC50 = 17.3 ?M).1 It reduces intracellular levels of GMP, GDP, and GTP, induces sporulation, and inhibits growth and cell wall synthesis in B. subtilis.2,3,4 It also reverses inhibition of aerial mycelium formation in Streptomyces grown in the presence of excess nutrients.5
1.Nakamura, J., and Lou, L.Biochemical characterization of human GMP synthetaseJ. Biol. Chem.270(13)7347-7353(1995) 2.Uratani, B., Lopez, J.M., and Freese, E.Effect of decoyinine on peptidoglycan synthesis and turnover in Bacillus subtilisJ. Bacteriol.154(1)261-268(1983) 3.Zain-ul-abedin, Lopez, J.M., and Freese, E.Induction of bacterial differentiation by adenine- and adenosine-analogs and inhibitors of nucleic acid synthesisNucleos. Nucleot.2(3)257-274(1983) 4.Bai, U., Lewandoski, M., Dubnau, E., et al.Temporal regulation of the Bacillus subtilis early sporulation gene spo0FJ. Bacteriol.172(9)5432-5439(1990) 5.Ochi, K.A decrease in GTP content is associated with aerial mycelium formation in Streptomyces MA406-A-1J. Gen. Microbiol.132(2)299-305(1986)
| Cas No. | 2004-04-8 | SDF | |
| 别名 | 德夸菌素 | ||
| Canonical SMILES | C=C(O1)[C@@H](O)[C@@H](O)[C@]1(CO)N2C=NC3=C(N)N=CN=C32 | ||
| 分子式 | C11H13N5O4 | 分子量 | 279.25 |
| 溶解度 | Soluble in DMSO | 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 | 3.581 mL | 17.9051 mL | 35.8102 mL |
| 5 mM | 0.7162 mL | 3.581 mL | 7.162 mL |
| 10 mM | 0.3581 mL | 1.7905 mL | 3.581 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。
Efficient biosynthesis of nucleoside cytokinin Angustmycin A containing an unusual sugar system
Nat Commun 2021 Nov 17;12(1):6633.PMID:34789759DOI:10.1038/s41467-021-26928-y.
Angustmycin A has anti-mycobacterial and cytokinin activities, and contains an intriguing structure in which an unusual sugar with C5'-C6' dehydration is linked to adenine via an N-glycosidic bond. However, the logic underlying the biosynthesis of this molecule has long remained obscure. Here, we address Angustmycin A biosynthesis by the full deciphering of its pathway. We demonstrate that AgmD, C, A, E, and B function as D-allulose 6-phosphate 3-epimerase, D-allulose 6-phosphate pyrophosphokinase, adenine phosphoallulosyltransferase, phosphoribohydrolase, and phosphatase, respectively, and that these collaboratively catalyze the relay reactions to biosynthesize angustmycin C. Additionally, we provide evidence that AgmF is a noncanonical dehydratase for the final step to Angustmycin A via a self-sufficient strategy for cofactor recycling. Finally, we have reconstituted the entire six-enzyme pathway in vitro and in E. coli leading to Angustmycin A production. These results expand the enzymatic repertoire regarding natural product biosynthesis, and also open the way for rational and rapid discovery of other angustmycin related antibiotics.
Pharmacological targeting of guanosine monophosphate synthase suppresses melanoma cell invasion and tumorigenicity
Cell Death Differ 2015 Nov;22(11):1858-64.PMID:25909885DOI:10.1038/cdd.2015.47.
Malignant melanoma possesses one of the highest metastatic potentials among human cancers. Acquisition of invasive phenotypes is a prerequisite for melanoma metastases. Elucidation of the molecular mechanisms underlying melanoma invasion will greatly enhance the design of novel agents for melanoma therapeutic intervention. Here, we report that guanosine monophosphate synthase (GMPS), an enzyme required for the de novo biosynthesis of GMP, has a major role in invasion and tumorigenicity of cells derived from either BRAF(V600E) or NRAS(Q61R) human metastatic melanomas. Moreover, GMPS levels are increased in metastatic human melanoma specimens compared with primary melanomas arguing that GMPS is an attractive candidate for anti-melanoma therapy. Accordingly, for the first time we demonstrate that Angustmycin A, a nucleoside-analog inhibitor of GMPS produced by Streptomyces hygroscopius efficiently suppresses melanoma cell invasion in vitro and tumorigenicity in immunocompromised mice. Our data identify GMPS as a powerful driver of melanoma cell invasion and warrant further investigation of Angustmycin A as a novel anti-melanoma agent.
Effect of Decoyinine on peptidoglycan synthesis and turnover in Bacillus subtilis
J Bacteriol 1983 Apr;154(1):261-8.PMID:6403504DOI:10.1128/jb.154.1.261-268.1983.
The sporulation of Bacillus subtilis can be induced in the presence of amino acids and glucose by partially depriving the cells of guanine nucleotides. This can be achieved, e.g., by the addition of Decoyinine, a specific inhibitor of GMP synthetase. To determine the effect of this and other inhibitors on cell wall synthesis, we measured in their presence the incorporation of acetylglucosamine into acid-precipitable material. The rate of wall synthesis decreased by 50% within 5 min after Decoyinine addition; this decrease was prevented by the presence of guanosine. A comparison with the effects of other inhibitors of cell wall synthesis indicated that Decoyinine inhibited the final portion of the cell wall biosynthetic pathway, i.e., after the steps inhibited by bacitracin or vancomycin. Decoyinine addition also prevented cellular autolysis and cell wall turnover. It is not known whether these two effects of Decoyinine on cell wall synthesis are causally related.
Sporulation of Streptomyces venezuelae in submerged cultures
J Gen Microbiol 1990 Mar;136(3):581-8.PMID:2391493DOI:10.1099/00221287-136-3-581.
Shaken cultures of Streptomyces venezuelae ISP5230 in minimal medium with galactose and ammonium sulphate as carbon and nitrogen sources, respectively, showed extensive sporulation after 72 h incubation at 37 degrees C. The spores formed in these cultures resembled aerial spores in their characteristics. The ability of the spores to withstand lysozyme treatment was used to monitor the progress of sporulation in cultures and to determine the physiological requirements for sporulation. In media containing ammonium sulphate as the nitrogen source, galactose was the best of six carbon sources tested. With galactose S. venezuelae ISP5230 sporulated when supplied with any of several nitrogen sources; however, an excess of nitrogen source was inhibitory. In cultures containing galactose and ammonium sulphate, sporulation was suppressed by a peptone supplement. The onset of sporulation was accompanied by a drop in intracellular GTP content. When Decoyinine, an inhibitor of GMP synthase, was added to a medium containing starch and ammonium sulphate, a slight increase in sporulation was seen after 2 d. The suppression of sporulation by peptone in liquid or agar cultures was not reversed by addition of Decoyinine. A hypersporulating mutant of S. venezuelae ISP5230 was altered in its ability to assimilate sugars. In cultures containing glucose the mutant sporulated more profusely than did the wild-type and did not acidify the medium to the same extent. However, the suppressive effect of glucose on sporulation was not merely a secondary result of acid accumulation.
Effect of Decoyinine on the regulation of alpha-amylase synthesis in Bacillus subtilis
J Bacteriol 1987 Dec;169(12):5867-9.PMID:3119574DOI:10.1128/jb.169.12.5867-5869.1987.
Decoyinine, an inhibitor of GMP synthetase, allows sporulation in Bacillus subtilis to initiate and proceed under otherwise catabolite-repressing conditions. The effect of Decoyinine on alpha-amylase synthesis in B. subtilis, an event which exhibits regulatory features resembling sporulation initiation, was examined. Decoyinine did not overcome catabolite repression of alpha-amylase synthesis in a wild-type strain of B. subtilis but did cause premature and enhanced synthesis in a mutant strain specifically blocked in catabolite repression of alpha-amylase synthesis. Decoyinine had no effect on alpha-amylase enzymatic activity. Thus, it appears that the catabolite control mechanisms governing alpha-amylase synthesis and sporulation in B. subtilis differ in their responses to Decoyinine and hence must consist at least partially of separate components.