DUPA
目录号 : GC34563
DUPA是一种谷氨酸脲，在药物耦联中作为靶向部分，可选择靶向性地将细胞毒性药物递送到前列腺癌细胞。
Cas No.:302941-52-2
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
DUPA, belongs to a class of glutamate ureas, is used as the targeting moiety in drug conjugate to selectively deliver cytotoxic drugs to prostate cancer cells[1][2].
DUPA is used as the targeting moiety to actively deliver Docetaxel (DTX) for treatment of prostate-specific membrane antigen (PSMA) expressing prostate cancer[1]. The DUPA-indenoisoquinoline conjugate exhibits an IC50 in the low nanomolar range in 22RV1 cell cultures[2].
The DUPA-indenoisoquinoline conjugate induces a complete cessation of tumor growth with no toxicity, as determined by loss of body weight and death of treated mice[2].
[1]. Peng ZH, et al. Spacer length impacts the efficacy of targeted docetaxel conjugates in prostate-specific membrane antigen expressing prostate cancer. J Drug Target. 2013 Dec;21(10):968-80. [2]. Roy J, et al. DUPA conjugation of a cytotoxic indenoisoquinoline topoisomerase I inhibitor for selective prostate cancer cell targeting. J Med Chem. 2015 Apr 9;58(7):3094-103.
| Cas No. | 302941-52-2 | SDF | |
| Canonical SMILES | O=C(N[C@](CCC(O)=O)([H])C(O)=O)N[C@](CCC(O)=O)([H])C(O)=O | ||
| 分子式 | C11H16N2O9 | 分子量 | 320.25 |
| 溶解度 | Water : ≥ 150 mg/mL (468.38 mM), DMSO : ≥ 300 mg/mL (936.77 mM) | 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 | 3.1226 mL | 15.6128 mL | 31.2256 mL |
| 5 mM | 0.6245 mL | 3.1226 mL | 6.2451 mL |
| 10 mM | 0.3123 mL | 1.5613 mL | 3.1226 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。
Regulation of Phosphoribosyl-Linked Serine Ubiquitination by Deubiquitinases DUPA and DupB
Mol Cell 2020 Jan 2;77(1):164-179.e6.PMID:31732457DOI:10.1016/j.molcel.2019.10.019.
The family of bacterial SidE enzymes catalyzes non-canonical phosphoribosyl-linked (PR) serine ubiquitination and promotes infectivity of Legionella pneumophila. Here, we describe identification of two bacterial effectors that reverse PR ubiquitination and are thus named deubiquitinases for PR ubiquitination (DUPs; DUPA and DupB). Structural analyses revealed that DUPA and SidE ubiquitin ligases harbor a highly homologous catalytic phosphodiesterase (PDE) domain. However, unlike SidE ubiquitin ligases, DUPA displays increased affinity to PR-ubiquitinated substrates, which allows DUPA to cleave PR ubiquitin from substrates. Interfering with DupA-ubiquitin binding switches its activity toward SidE-type ligase. Given the high affinity of DUPA to PR-ubiquitinated substrates, we exploited a catalytically inactive DUPA mutant to trap and identify more than 180 PR-ubiquitinated host proteins in Legionella-infected cells. Proteins involved in endoplasmic reticulum (ER) fragmentation and membrane recruitment to Legionella-containing vacuoles (LCV) emerged as major SidE targets. The global map of PR-ubiquitinated substrates provides critical insights into host-pathogen interactions during Legionella infection.
Novel virulence factor DUPA of Helicobacter pylori as an important risk determinant for disease manifestation: An overview
World J Gastroenterol 2020 Aug 28;26(32):4739-4752.PMID:32921954DOI:10.3748/wjg.v26.i32.4739.
Helicobacter pylori (H. pylori) is a microaerophilic, Gram-negative, human gastric pathogen found usually in the mucous lining of stomach. It infects more than 50% of the world's population and leads to gastroduodenal diseases. The outcome of disease depends on mainly three factors: Host genetics, environment and bacterial factors. Among these, bacterial virulence factors such as cagA, vacA are well known for their role in disease outcomes. However, based on the global epidemiological results, none of the bacterial virulence (gene) factors was found to be associated with particular diseases like duodenal ulcer (DU) in all populations. Hence, substantial importance has been provided for research in strain-specific genes outside the cag pathogenicity island, especially genes located within the plasticity regions. DUPA found within the plasticity regions was first demonstrated in 2005 and was proposed for duodenal ulcer development and reduced risk of gastric cancer in certain geographical regions. Due to the discrepancies in report from different parts of the world in DU development related to H. pylori virulence factor, DUPA became an interesting area of research in elucidating the role of this gene in the disease progression. In this review, we shed light on the detailed information available on the polymorphisms in DUPA and their clinical relevance. We have critically appraised several pertinent studies on DUPA and discussed their merits and shortcomings. This review also highlights DUPA gene as an important biomarker for DU in certain populations.
Role of DUPA in virulence of Helicobacter pylori
World J Gastroenterol 2016 Dec 14;22(46):10118-10123.PMID:28028359DOI:10.3748/wjg.v22.i46.10118.
Helicobacter pylori (H. pylori) is a gastric human pathogen associated with acute and chronic gastritis, 70% of all gastric ulcers, 85% of all duodenal ulcers, and both forms of stomach cancer, mucosal-associated lymphoid tissue (MALT) lymphoma and adenocarcinoma. Recently, attention has focused on possible relationship between presence of certain virulence factor and H. pylori-associated diseases. Some contradictory data between this bacterium and related disorders has been observed since not all the colonized individuals develop to severe disease. The reported diseases plausibility related to H. pylori specific virulence factors became an interesting story about this organism. Although a number of putative virulence factors have been identified including cytotoxin-associated gene a (cagA) and vacA, there are conflicting data about their actual participation as specific risk factor for H. pylori-related diseases. Duodenal ulcer promoting gene a (DUPA) is a virulence factor of H. pylori that is highly associated with duodenal ulcer development and reduced risk of gastric cancer. The prevalence of DUPA in H. pylori strains isolated from western countries is relatively higher than in H. pylori strains from Asian countries. Current confusing epidemiological reports will continue unless future sophisticated and molecular studies provide data on functional and complete DUPA cluster in H. pylori infected individuals. This paper elucidates available knowledge concerning role of DUPA in virulence of H. pylori after a decade of its discovery.
Helicobacter pylori virulence DUPA gene: risk factor or protective factor?
Braz J Microbiol 2021 Dec;52(4):1921-1927.PMID:34255308DOI:10.1007/s42770-021-00553-9.
Helicobacter pylori is the etiological agent of chronic gastritis, peptic ulcer, and gastric cancer. The duodenal ulcer-promoting gene DUPA, which is located in the plasticity region of the H. pylori genome, is homologous to the virB gene which encodes a type IV secretion protein in Agrobacterium tumefaciens. Studies have shown associations between H. pylori dupA-positive strains and gastroduodenal diseases. However, whether DUPA acts as a risk factor or protective factor in these diseases remains unclear. Therefore, in this study, we aimed to verify the presence of the DUPA gene in infectious H. pylori strains in the Brazilian mid-west and to investigate its association with the clinical outcomes of patients with dyspepsia. Additionally, the phylogenetic origin of the strains was determined. Gastric biopsies from 117 patients with dyspepsia were analyzed using histological and molecular techniques. The hpx gene (16S rRNA) was used to screen for H. pylori infection, and positive samples were then subjected to DUPA gene detection and sequencing. The estimated prevalence of H. pylori infection was 64.1%, with the DUPA gene being detected in a high proportion of infectious strains (70.7%). Furthermore, a risk analysis revealed that for women, a dupA-positive H. pylori infection increased the chance of developing gastritis by twofold. The partial DUPA sequences from isolated infectious strains in this work are similar to those of strains isolated in westerns countries. This study provides useful insights for understanding the role of the H. pylori DUPA gene in disease development.
DUPA + H. pylor i reduces diversity of gastric microbiome and increases risk of erosive gastritis
Front Cell Infect Microbiol 2023 Mar 17;13:1103909.PMID:37009501DOI:10.3389/fcimb.2023.1103909.
Helicobacter pylori is believed to induce gastropathy; however, the exact pathogenic molecules involved in this process have not been elucidated. Duodenal ulcer promoting gene A (DUPA) is a virulence factor with a controversial role in gastric inflammation and carcinogenesis. To explore and confirm the function of DUPA in gastropathy from the perspective of the microbiome, we investigated the microbial characteristics of 48 gastritis patients through 16S rRNA amplicon sequencing. In addition, we isolated 21 H. pylori strains from these patients and confirmed the expression of DUPA using PCR and qRT-PCR. Bioinformatics analysis identified diversity loss and compositional changes as the key features of precancerous lesions in the stomach, and H. pylori was a characteristic microbe present in the stomach of the gastritis patients. Co-occurrence analysis revealed that H. pylori infection inhibits growth of other gastric inhabiting microbes, which weakened the degradation of xenobiotics. Further analysis showed that DUPA+ H. pylori were absent in precancerous lesions and were more likely to appear in erosive gastritis, whereas dupA- H. pylori was highly abundant in precancerous lesions. The presence of DUPA in H. pylori caused less disturbance to the gastric microbiome, maintaining the relatively richness of gastric microbiome. Overall, our findings suggest that high DUPA expression in H. pylori is correlated with a high risk of erosive gastritis and a lower level of disturbance to the gastric microbiome, indicating that DUPA should be considered a risk factor of erosive gastritis rather than gastric cancer.