Nogalamycin
(Synonyms: 诺拉霉素) 目录号 : GC44438
An anthracycline with anticancer activity
Cas No.:1404-15-5
Sample solution is provided at 25 µL, 10mM.
;)
,-1-7$$$37316672.jpg');)
;)
;)
$$$36806353.jpg');)
;33(7)%EF%BC%9A546-561$$$37156877.jpg');)
;)
;)
;)
%201124-1138.$$$35908550.jpg');)
%20766-780.$$$37100057.jpg');)
%20418-432.$$$36893736.jpg');)
%EF%BC%9A-240-255.$$$35108512.jpg');)
533-545$$$36543525.jpg');)
%201-13.$$$36600053.jpg');)
;)
Quality Control & SDS
- View current batch:
- Purity: >95.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Nogalamycin is an anthracycline originally isolated from S. nogalater and a DNA-intercalating agent. It inhibits the DNA-unwinding and ATPase activities of P. falciparum DNA helicase 60 (IC50s = 2 and 0.5 μM, respectively) and the DNA cleavage activity of vaccinia virus topoisomerase (IC50 = 0.7 μM). Nogalamycin also inhibits the growth of MCF-7 and MDA-MB-231 human breast cancer cells (IC50s = 0.242 and 0.37 μM, respectively).
| Cas No. | 1404-15-5 | SDF | |
| 别名 | 诺拉霉素 | ||
| Canonical SMILES | OC1=C(C(C(C(O)=CC2=C3O[C@@]4([H])[C@@H](O)[C@H](N(C)C)[C@@H](O)[C@@]2(O4)C)=C3C5=O)=O)C5=CC6=C1[C@@H](O[C@@]7([H])[C@H](OC)[C@@](OC)(C)[C@@H](OC)[C@H](C)O7)C[C@](C)(O)[C@@H]6C(OC)=O | ||
| 分子式 | C39H49NO16 | 分子量 | 787.8 |
| 溶解度 | DMF: Soluble,DMSO: Soluble,Ethanol: soluble,Methanol: Soluble | 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。 |
||
| 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 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 1.2694 mL | 6.3468 mL | 12.6936 mL |
| 5 mM | 0.2539 mL | 1.2694 mL | 2.5387 mL |
| 10 mM | 0.1269 mL | 0.6347 mL | 1.2694 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。
DNA-nogalamycin interactions
Biochemistry 1991 Feb 5;30(5):1364-72.PMID:1991116DOI:10.1021/bi00219a029.
The anthracycline antibiotic Nogalamycin differs from the more common daunomycin-type anthracyclines by substitution on both ends of the intercalating chromophore, giving Nogalamycin the approximate shape of a dumbbell. The chromophore of daunomycin is substituted on only one end. In Nogalamycin, the positively charged amino sugar substituent of daunomycin is replaced by an uncharged nogalose sugar and a methyl ester group. The other end of Nogalamycin, where daunomycin is unsubstituted, is fused to a bicyclo amino sugar with a positively charged dimethylamino group. Much larger DNA fluctuations are required for intercalative entry of Nogalamycin than for entry of daunomycin. This report describes the X-ray crystal structure of the complex between Nogalamycin and the self-complementary DNA hexamer d(me5CGTsAme5CG). The DNA contains cytosines methylated at the 5-positions and a phosphorothioate linkage at the TpA step. Nogalamycin intercalates at the terminal CpG steps and interacts with both strands in both grooves of the DNA. Large conformational adjustments in both Nogalamycin and the DNA are necessary to form a stable, intercalative complex. The interactions of the bases with the Nogalamycin substituents lead to sliding of bases relative to each other along the normal to Watson-Crick hydrogen bonds. The planarities of base pairs surrounding the intercalation site are distorted. The backbones of the two strands are distorted asymmetrically by Nogalamycin with large deviations from standard B-DNA geometry. The complex between Nogalamycin and DNA illustrates the conformational flexibility of DNA. The hydrogen-bonding interactions between Nogalamycin and DNA do not suggest a sequence-specific binding of the drug, although additional secondary effects might lead to differences between various intercalation sites.
The snogI Gene is Necessary for the Proper Functioning of the Nogalamycin Biosynthesis Pathway
Indian J Microbiol 2021 Dec;61(4):467-474.PMID:34744202DOI:10.1007/s12088-021-00941-7.
Anthracycline drugs have multifunctional molecular structures, and small changes in the structure of the glycosyls around the chromophore affect their mechanism of action, pharmacokinetics, toxicity, anti-tumor activity, and many other significant parameters. DnrJ has a similar function to snogI but inverse stereoselectivity. SnogI encoding amino transferase was substituted for DnrJ for the purpose of obtaining Nogalamycin analogues. We inactivated the snogI gene encoding an aminotransferase responsible for the formation of nogalamine and introduced the dnrJ gene encoding an aminotransferase responsible for the formation of daunosamine. We obtained the recombinant strain mLMX-3-100, in which the production of Nogalamycin was disrupted. Interestingly, contrary to our predictions, no epi-nogalamycin was produced; nevertheless, the present study shows that the snogI gene is necessary for the proper functioning of the Nogalamycin biosynthesis pathway. These data may provide a reference for further illustration of Nogalamycin biosynthesis and its modification by way of combinatorial biosynthesis.biosynthesis and its modification by way of combinatorial biosynthesis.
The biochemical pharmacology of Nogalamycin and its derivatives
Pharmacol Ther 1991;51(2):239-55.PMID:1838416DOI:10.1016/0163-7258(91)90080-6.
This review assimilates up-to-date information on the biochemical pharmacology of Nogalamycin and selected derivatives that have shown good biological activities and/or received a relatively detailed investigation. The structure and chemical preparation of these derivatives from Nogalamycin is described and the nomenclature which has been rather perplexing in the literature is clarified. The interaction of this class of compounds, particularly Nogalamycin, with DNA is extensively reviewed. The biochemical mechanism of action of Nogalamycin and its structurally closely-related derivatives is described. Among Nogalamycin derivatives, menogaril showed distinct biochemical effects as well as superior cytotoxicity and antitumor activity and also proved to be effective against breast cancer clinically.
Structure of Nogalamycin bound to a DNA hexamer
Proc Natl Acad Sci U S A 1990 Mar;87(6):2225-9.PMID:2315315DOI:10.1073/pnas.87.6.2225.
The anthracycline antibiotic Nogalamycin, which binds to DNA, is composed of a planar aglycone substituted on each end to form an unusual dumbbell-shaped molecule. At one end Nogalamycin contains an uncharged nogalose sugar and a methyl ester. At the other end Nogalamycin contains a positively charged bicyclo amino sugar. We report the crystal structure of Nogalamycin bound to the self-complementary DNA hexamer d(m5CGTsAm5CG). In this complex, the cytosines are methylated at the 5 position and the DNA contains a phosphorothioate linkage at the TpA step. Two Nogalamycin molecules bind to the 6-base-pair fragment of double-helical DNA. The drug has threaded between the phosphodiester backbones with three aromatic rings intercalated within the DNA. In the major groove, the bicyclo amino sugar forms two direct hydrogen bonds to span a CG base pair and interacts indirectly with the next base pair of the duplex via a water-mediated hydrogen bond. In the minor groove, a carbonyl oxygen of Nogalamycin forms a hydrogen bond directly to N2 of a guanine. The DNA base pairs are severely buckled by up to 26 degrees and are also distorted in directions perpendicular to the Watson-Crick hydrogen bonds. This complex illustrates the deformable nature of DNA.
Inactivation and identification of three genes encoding glycosyltransferase required for biosynthesis of Nogalamycin
Biotechnol Appl Biochem 2015 Nov-Dec;62(6):765-71.PMID:25524457DOI:10.1002/bab.1332.
Nogalamycin is an anthracycline antitumor antibiotic, consisting of the aromatic aglycone attached with a nogalose and a nogalamine. At present, the biosynthesis pathway of Nogalamycin, especially the glycosylation mechanism of the two deoxysugar moieties, had still not been extensively investigated in vivo. In this study, we inactivated the three glycotransferase genes in the nogalamycin-produced strain, and investigated the function of these genes by analyzing the metabolites profiles in the fermentation broth. The in-frame deletion of snogD and disruption of snogE abolished the production of Nogalamycin completely, indicating that the gene products of snogD and snogE are essential to the biosynthesis of Nogalamycin. On the other hand, in-frame deletion of snogZ does not abolish the production of Nogalamycin, but production yield was reduced to 28% of the wild type, implying that snogZ gene may involved in the activation of other glycotransferases in Nogalamycin biosynthesis. This study laid the foundation of modification of Nogalamycin biosynthesis/production by genetic engineering methods.