固相兼容的基于西兰的可切割连接器可以实现定制的同位素定量化疗法
Nikolas R Burton1,2, Daniel A Polasky3, Flowreen Shikwana1,2
1Department of Biological Chemistry, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California 90095, United States.
Journal of the American Chemical Society
|September 22, 2023
概括
我们开发了一种新的化学蛋白质组学方法, 这种方法提高了样品制备的效率,并确定了新型的氨酸 - 配体相互作用,如FCCP作为电友.
科学领域:
- 蛋白质组学
- 化学生物学
- 药物发现
背景情况:
- 基于质谱的化学蛋白质组学对于功能生物学和药物发现至关重要.
- 现有方法在试剂合成和样品制备吞吐量方面面临挑战.
研究的目的:
- 建立一种新的化学蛋白质组工作流程,即基于西兰的可裂变同位素标记蛋白质组 (sCIP),以克服当前的局限性.
- 为了实现高通量,高效的样本制备和分析,以确定蛋白质-连接物相互作用.
主要方法:
- 开发了一种可扩展的dialkoxydiphenylsilane甲基基 (DADPS-Fmoc) 保护的氨基酸合成方法.
- 创建可定制的,同位素标记的,和化学分离的生物素捕获试剂.
- 采用MS1/MS2量化实现的sCIP,具有用于早期标记和聚合的点击组装等离子标签,可实现六倍复合.
主要成果:
- 该方法简化了样本准备,增加了产量和数据覆盖范围.
- 与FragPipe分析相结合,sCIP确定了已知和新发现的氨酸配体对.
- 发现线粒体解剂FCCP作为共价可逆的氨酸反应电.
结论:
- 该方法为化学蛋白质组提供了一个强大而高效的平台.
- 这种方法通过全面识别囊 - 连接物相互作用,促进了功能生物学和药物发现.
- 这些发现突显了FCCP作为一种氨酸反应电友的新作用机制.
相关概念视频
Relative Strengths of Conjugate Acid-Base Pairs
Brønsted-Lowry acid-base chemistry is the transfer of protons; thus, logic suggests a relation between the relative strengths of conjugate acid-base pairs. The strength of an acid or base is quantified in its ionization constant, Ka or Kb, which represents the extent of the acid or base ionization reaction. For the conjugate acid-base pair HA / A−, the ionization equilibrium equations and ionization constant expressions are
Titration Calculations: Strong Acid - Strong Base
Calculating pH for Titration Solutions: Strong Acid/Strong Base
A titration is carried out for 25.00 mL of 0.100 M HCl (strong acid) with 0.100 M of a strong base NaOH. The pH at different volumes of added base solution can be calculated as follows:
(a) Titrant volume = 0 mL. The solution pH is due to the acid ionization of HCl. Because this is a strong acid, the ionization is complete and the hydronium ion molarity is 0.100 M. The pH of the solution is then:
A titration is carried out for 25.00 mL of 0.100 M HCl (strong acid) with 0.100 M of a strong base NaOH. The pH at different volumes of added base solution can be calculated as follows:
(a) Titrant volume = 0 mL. The solution pH is due to the acid ionization of HCl. Because this is a strong acid, the ionization is complete and the hydronium ion molarity is 0.100 M. The pH of the solution is then:
Leveling Effect and Non-Aqueous Acid-Base Solutions
This lesson defines the leveling effect in acidic and basic solutions and its role in aqueous and non-aqueous solutions. It is essential to understand the competing nature of various species in a chemical system.
The Leveling Effect of a Solvent
A generic acid (HA) reacts with the generic base (B-) to yield the corresponding conjugate base (A-) and conjugate acid (HB):
The Leveling Effect of a Solvent
A generic acid (HA) reacts with the generic base (B-) to yield the corresponding conjugate base (A-) and conjugate acid (HB):
Recrystallization: Solid–Solution Equilibria
Recrystallization is a purification technique used to separate impurities from solid compounds. In this technique, no chemical reactions occur. Instead, it exploits physical properties only, specifically, the solubility differences between the desired compound and impurities, either at a single temperature or at different temperatures, and under other selected conditions. The solid-solution equilibrium (solubility equilibrium) of each component in the solution represents a binary phase...
Titration of Polyprotic Base with a Strong Acid
The titration of a polyprotic base such as sodium carbonate with a strong acid such as hydrochloric acid results in two equivalence points on the titration curve. At the first equivalence point, the carbonate ions in the base are completely converted to bicarbonate ions. The second equivalence point corresponds to the complete conversion of bicarbonate ions to carbonic acid, which dissociates into carbon dioxide and water. The region before the first equivalence point corresponds to the...
Complexometric Titration: Ligands
Different monodentate and polydentate ligands are used as complexing agents in complexometric titration reactions. The formation of complexes by mono- and bidentate ligands involves two or more intermediate steps, limiting their use as complexing agents. In comparison, polydentate ligands can form complexes with metal ions in a single-step process, facilitating sharper end points. This means polydentate ligands, such as amino carboxylic acid derivatives, are most commonly employed in...


