化学诱导的乙烯基基酸电用于-生物结合
Alice L Baumann1,2, Sergej Schwagerus1,2, Kevin Broi2
1Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Robert-Rössle-Straße 10, 13125 Berlin, Germany.
Journal of the American Chemical Society
|April 28, 2020
概括
我们研发出一种新型的囊选择性电友, 这种方法可以通过简单的合成途径实现稳定的蛋白质-蛋白质链接.
科学领域:
- 生物化学
- 有机化学
- 化学生物学
背景情况:
- 选择性蛋白质标签对于化学生物学来说至关重要.
- 现有的蛋白质结合方法在稳定性和范围上可能受到限制.
研究的目的:
- 引入乙烯酸酸盐作为新型的氨酸选择性电友.
- 开发一种简单的合成方法来制备和应用它们.
- 为了证明它们在蛋白质标记和稳定的蛋白质-蛋白质结合中的有用性.
主要方法:
- 通过二硫化物中间体从核性硫醇合成乙烯酸.
- 在酸性条件下用乙烯酸替代二硫化物.
- 应用对单克隆抗体和特定位点蛋白质结合的标记协议.
主要成果:
- 成功合成具有优良的氨酸选择性的乙烯基酸.
- 显示了单克隆抗体trastuzumab的标记.
- 形成稳定,不可水解的基酸联二维基和基-α-同核素结合物.
- 这种 ubiquitin-α-synuclein 结合物在酶上被 ubiquitin 化.
结论:
- 乙烯基基酸盐代表了一种用于氨酸导向生物结合的多功能新类电友.
- 开发的合成协议是高效的,适用于复杂的蛋白质.
- 这种方法可以创建稳定的蛋白结合物,在药物输送和理解生物通路方面具有潜在的应用.
相关概念视频
02:33Preparation and Reactions of Thiols
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Thiols are prepared using the hydrosulfide anion as a nucleophile in a nucleophilic substitution reaction with alkyl halides. For instance, bromobutane reacts with sodium hydrosulfide to give butanethiol.
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02:26Preparation and Reactions of Sulfides
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Sulfides are the sulfur analog of ethers, just as thiols are the sulfur analog of alcohol. Like ethers, sulfides also consist of two hydrocarbon groups bonded to the central sulfur atom. Depending upon the type of groups present, sulfides can be symmetrical or asymmetrical. Symmetrical sulfides can be prepared via an SN2 reaction between 2 equivalents of an alkyl halide and one equivalent of sodium sulfide.
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01:26Photochemical Electrocyclic Reactions: Stereochemistry
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The absorption of UV–visible light by conjugated systems causes the promotion of an electron from the ground state to the excited state. Consequently, photochemical electrocyclic reactions proceed via the excited-state HOMO rather than the ground-state HOMO. Since the ground- and excited-state HOMOs have different symmetries, the stereochemical outcome of electrocyclic reactions depends on the mode of activation; i.e., thermal or photochemical.
Selection Rules: Photochemical Activation
Selection Rules: Photochemical Activation
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01:24Acetals and Thioacetals as Protecting Groups for Aldehydes and Ketones
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Acetals are formed by reacting two equivalents of alcohol with carbonyl compounds like aldehydes or ketones. Acetals are unaffected by bases, nucleophiles, oxidizing agents, and reducing agents. They serve as protecting groups for aldehydes and ketones. Acetals can be easily formed and also easily removed via mild acid hydrolysis.
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
In the presence of multiple functional groups, when selective reduction of one group over the other is desired, groups like aldehydes and ketones that form acetals...
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02:35Electrophilic Addition to Alkynes: Hydrohalogenation
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01:08Conjugate Addition of Enolates: Michael Addition
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The attack of a nucleophile at the β carbon of an α,β-unsaturated carbonyl compound is called conjugate addition. Conjugate addition reactions of active methylene compounds, such as β-diketones, β-keto esters, β-keto nitriles, and α-nitro ketones, are called Michael addition reactions.
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