Formycin A
(Synonyms: 间型霉素A,NSC 102811) 目录号 : GC63646
Formycin A (NSC 102811) 是一种嘌呤核苷抗生素，一种有效的人类免疫缺陷病毒 1 型 (HIV-1) 的抑制剂，EC50 为 10 μM。Formycin A 显示抗肿瘤和抗病毒活性。
Cas No.:6742-12-7
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
Formycin A (NSC 102811), a purine nucleoside antibiotic, is a potent human immunodeficiency virus type 1 (HIV-1) inhibitor with an EC50 of 10 μM. Formycin A shows antitumor and antiviral activities[1][2].
Formycin A (NSC 102811; 1 μM, 5 μM, 10 μM) antagonizes Zidovudine (AZT; a dideoxynucleoside chain terminator).
[1]. Dapp MJ , et al. Discovery of novel ribonucleoside analogs with activity against human immunodeficiency virus type 1.J Virol. 2014 Jan;88(1):354-63.
[2]. Zhang M, et al. Comparative Investigation into Formycin A and Pyrazofurin A Biosynthesis Reveals Branch Pathways for the Construction of C-Nucleoside Scaffolds. Appl Environ Microbiol. 2020 Jan 7;86(2).
| Cas No. | 6742-12-7 | SDF | |
| 别名 | 间型霉素A,NSC 102811 | ||
| 分子式 | C10H13N5O4 | 分子量 | 267.24 |
| 溶解度 | 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 | 3.742 mL | 18.7098 mL | 37.4195 mL |
| 5 mM | 0.7484 mL | 3.742 mL | 7.4839 mL |
| 10 mM | 0.3742 mL | 1.871 mL | 3.742 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。
Comparative Investigation into Formycin A and Pyrazofurin A Biosynthesis Reveals Branch Pathways for the Construction of C-Nucleoside Scaffolds
Appl Environ Microbiol 2020 Jan 7;86(2):e01971-19.PMID:31676476DOI:10.1128/AEM.01971-19.
Formycin A (FOR-A) and pyrazofurin A (PRF-A) are purine-related C-nucleoside antibiotics in which ribose and a pyrazole-derived base are linked by a C-glycosidic bond. However, the logic underlying the biosynthesis of these molecules has remained largely unexplored. Here, we report the discovery of the pathways for FOR-A and PRF-A biosynthesis from diverse actinobacteria and propose that their biosynthesis is likely initiated by a lysine N6-monooxygenase. Moreover, we show that forT and prfT (involved in FOR-A and PRF-A biosynthesis, respectively) mutants are correspondingly capable of accumulating the unexpected pyrazole-related intermediates 4-amino-3,5-dicarboxypyrazole and 3,5-dicarboxy-4-oxo-4,5-dihydropyrazole. We also decipher the enzymatic mechanism of ForT/PrfT for C-glycosidic bond formation in FOR-A/PRF-A biosynthesis. To our knowledge, ForT/PrfT represents an example of β-RFA-P (β-ribofuranosyl-aminobenzene 5'-phosphate) synthase-like enzymes governing C-nucleoside scaffold construction in natural product biosynthesis. These data establish a foundation for combinatorial biosynthesis of related purine nucleoside antibiotics and also open the way for target-directed genome mining of PRF-A/FOR-A-related antibiotics.IMPORTANCE FOR-A and PRF-A are C-nucleoside antibiotics known for their unusual chemical structures and remarkable biological activities. Deciphering the enzymatic mechanism for the construction of a C-nucleoside scaffold during FOR-A/PRF-A biosynthesis will not only expand the biochemical repertoire for novel enzymatic reactions but also permit target-oriented genome mining of FOR-A/PRF-A-related C-nucleoside antibiotics. Moreover, the availability of FOR-A/PRF-A biosynthetic gene clusters will pave the way for the rational generation of designer FOR-A/PRF-A derivatives with enhanced/selective bioactivity via synthetic biology strategies.
Identification of the Formycin A Biosynthetic Gene Cluster from Streptomyces kaniharaensis Illustrates the Interplay between Biological Pyrazolopyrimidine Formation and de Novo Purine Biosynthesis
J Am Chem Soc 2019 Apr 17;141(15):6127-6131.PMID:30942582DOI:10.1021/jacs.9b00241.
Formycin A is a potent purine nucleoside antibiotic with a C-glycosidic linkage between the ribosyl moiety and the pyrazolopyrimidine base. Herein, a cosmid is identified from the Streptomyces kaniharaensis genome library that contains the for gene cluster responsible for the biosynthesis of formycin. Subsequent gene deletion experiments and in vitro characterization of the forBCH gene products established their catalytic functions in formycin biosynthesis. Results also demonstrated that PurH from de novo purine biosynthesis plays a key role in pyrazolopyrimidine formation during biosynthesis of Formycin A. The participation of PurH in both pathways represents a good example of how primary and secondary metabolism are interlinked.
A synergistic effect of phosphate, pH and Phe159 substitution on the Formycin A association to the E. coli purine nucleoside phosphorylase
Biochimie 2018 May;148:80-86.PMID:29499297DOI:10.1016/j.biochi.2018.02.012.
A steady-state absorption and emission spectroscopy was used to create a comprehensive work and to study the interaction of the wild type Escherichia coli purine nucleoside phosphorylase and its mutants, PNPF159Y and PNPF159A, with a potent E. coli PNP inhibitor - Formycin A. The absorption and emission spectra were recorded in the presence and absence of the phosphate at the 50 mM concentration. From the collected sets of data dissociation constants (Kd), apparent dissociation constants (Kapp) and Hill's coefficients (h) were calculated. Additionally, the temperature dependence of the enzymes emission quenching at two temperatures, 10 °C and 25 °C, was examined. To verify the calculations, total difference absorption spectra were computed for all types of the complexes. A prominent quenching of the PNPF159Y emission indicates a complex formation, with the strongest association in the phosphate buffer, pH 7, relative to the wild type enzyme. On the other hand, results testify to a deterioration of the interactions in the E. coli PNP/PNPF159Y and Formycin A complexes in the presence of the phosphate, pH 8.3. Moreover, data obtained for the PNPF159A-FA complexes confirm a weak association of the FA to the mutant's active center.
The riddle of Formycin A insulinotropic action
Biochem Mol Med 1996 Feb;57(1):47-63.PMID:8812726DOI:10.1006/bmme.1996.0008.
Formycin A augments insulin release evoked by glucose (5.6 mm or more), this effect not being rapidly reversible. The mechanism responsible for the insulinotropic action of Formycin A was investigated in isolated pancreatic islets. It could not be ascribed to facilitation of glucose metabolism. On the contrary, Formycin A inhibited glucose oxidation, lowered ATP content, and impaired glucose-stimulated protein biosynthesis. The insulinotropic action of Formycin A was apparently attributable to its conversion to Formycin A 5'-triphosphate, both this process and the secretory response to Formycin A being abolished by the inhibitor of adenosine kinase 5-iodotubercidin. In agreement with the latter view, adenosine receptor antagonists such as 8-cyclopentyl-1, 3-dipropylxanthine and 3,7-dimethyl-1-propargylxanthine failed to suppress and, instead, augmented the insulinotropic action of Formycin A. Unexpectedly, however, Formycin A failed to decrease 86Rb efflux, this coinciding with a low efficiency of Formycin A 5'-triphosphate to inhibit KATP-channel activity in excised membranes and with the fact that Formycin A increased gliben-clamide-stimulated insulin release. The secretory response to Formycin A represented a Ca2+-dependent process suppressed in the absence of extracellular Ca2+ or presence of verapamil and associated with an increased net uptake of 45Ca. Nevertheless, the view that Formycin A exerts any major effect upon intracellular Ca2+ redistribution, protein kinase C activity, or cyclic AMP net production also met with objections such as the minor secretory effect of Formycin A in islets exposed to a high concentration of K+ in the presence of a diazoxide analog, the resistance of Formycin A insulinotropic action to bisindolylmaleimide, the poor increase of cyclic AMP content in formycin A-stimulated islets, and the pronounced enhancement by forskolin or theophylline of insulin release from islets exposed to Formycin A. It is concluded, therefore, that the mechanism of action of Formycin A in the pancreatic beta-cell remains to be elucidated.
Effects of a new adenosine deaminase inhibitor, isocoformycin, on toxicity, antitumor activity and tissue distribution of Formycin A and 9-beta-D-arabinofuranosyladenine
J Antibiot (Tokyo) 1980 Mar;33(3):303-9.PMID:7380742DOI:10.7164/antibiotics.33.303.
Single intraperitoneal and intravenous injections of isocoformycin at 1,200 mg/kg did not cause the death of mice. Isocoformycin which inhibited adenosine deaminase enhanced significantly the toxicity of Formycin A and ara-A at various combination ratios. Isocoformycin potentiated antitumor activity of Formycin A and ara-A against L1210 leukemia. Formycin A and ara-A disappeared rapidly from the blood and tissues and could not be found in any tissues even 0.5 hour after a single intraperitoneal injection. However, when used in combination with isocoformycin both were detected in the blood and tissues, especially at high concentration in liver and kidney. These indicate that the deamination of Formycin A and ara-A is blocked by isocoformycin in vivo.