作为选择Pt结合蛋白的有效降解剂的第一类金属PROTAC
Paul D O'Dowd1,2, Graeme P Sullivan3, Daniel A Rodrigues1
1Department of Chemistry, Royal College of Surgeons in Ireland, Dublin 2, Ireland. dgriffith@rcsi.ie.
概括
研究人员开发了第一个以为基础的蛋白解向化体 (Pt-PROTAC) 来降解特定的 (II) 结合蛋白. 这种新型的金属-PROTAC有效地向多发性骨髓瘤细胞中的硫素蛋白,显示出癌症治疗的潜力.
科学领域:
- 生物化学 生物化学
- 化学生物学 化学生物学
- 在瘤学瘤学.
背景情况:
- 针对蛋白质分解的嵌合体 (PROTACs) 是新兴的治疗方法.
- 针对细胞内蛋白质仍然是药物开发中的一个挑战.
- ((II) 化合物在癌症化疗中广泛使用.
研究的目的:
- 开发第一个使用金的金属PROTAC.
- 研究Pt-PROTAC在降解特定的Pt-II结合蛋白中的有效性.
- 探索金属-PROTACs在癌症治疗和蛋白质识别中的潜力.
主要方法:
- 一个新的Pt-PROTAC的设计和合成.
- 在多个髓瘤癌细胞系使用的体外降解试验.
- 目标蛋白的识别和验证.
主要成果:
- 该Pt-PROTAC成功降解了硫素-1和硫素还原酶-1.
- 癌细胞中标蛋白的选择性降解已被证明.
- 验证了金属PROTACs的概念验证.
结论:
- 金属-PROTACs代表了一类新的向蛋白质降解剂.
- 作为癌症治疗的化疗剂,pt-PROTACs显示出有前途.
- 这种方法可以帮助识别新的金属结合蛋白.
相关概念视频
Masking and Demasking Agents
2.5K
EDTA titrations may necessitate masking and demasking agents to temporarily protect a particular metal ion in a mixture from the EDTA reaction. These agents facilitate the sequential analysis of the metal ions by forming stable complexes with some—but not all—metal ions during certain steps.
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on...
There are many masking agents, such as cyanide, fluoride, triethanolamine, thiourea, and 2,3-bis(sulfanyl)propan-1-ol (formerly 2,3-dimercapto-1-propanol), with the masking agent chosen based on...
2.5K
Effects of EDTA on End-Point Detection Methods
286
Different methods, such as visual observance of metal-ion indicators, spectroscopic techniques, and potentiometric methods, can determine the endpoint of an EDTA titration.
In the visual method, metal-ion indicators (metallochromic dyes), which have distinct colors in their free and complex forms, are added to the mixture to signal the titration's end point. They form stable complexes with metal ions, but these complexes are weaker than the corresponding metal–EDTA complexes. As a...
In the visual method, metal-ion indicators (metallochromic dyes), which have distinct colors in their free and complex forms, are added to the mixture to signal the titration's end point. They form stable complexes with metal ions, but these complexes are weaker than the corresponding metal–EDTA complexes. As a...
286
EDTA: Chemistry and Properties
2.0K
Polydentate ligands are most widely used in complexometric titrations because they form more stable complexes with the metal ions than mono- or bidentate ligands due to the chelate effect. Examples of polydentate ligands are ethylenediaminetetraacetic acid (EDTA), crown ethers, and cryptands. The most important feature of optimal polydentate ligands is the ability to form 1:1 complexes in a single-step process. Amino carboxylic acid derivatives are frequently used as complexing agents. EDTA is...
2.0K
EDTA: Auxiliary Complexing Reagents
603
EDTA titrations are usually carried out in highly basic conditions, where the fully deprotonated form of EDTA, Y4−, actively complexes with the free metal ions in the solution. Several metal ions precipitate as hydrous oxide (hydroxides, oxides, or oxyhydroxides) under these conditions, lowering the concentration of free metal ions in the solution. For this reason, auxiliary complexing agents or ligands such as ammonia, tartrate, citrate, or triethanolamine are used in EDTA titrations to...
603
Extraction: Advanced Methods
469
Metal ions can be separated from one another by complexation with organic ligands–the chelating agent– to form uncharged chelates. Here, the chelating agent must contain hydrophobic groups and behave as a weak acid, losing a proton to bind with the metal. Since most organic ligands used in this process are insoluble or undergo oxidation in the aqueous phase, the chelating agent is initially added to the organic phase and extracted into the aqueous phase. The metal-ligand complex is...
469


