光介导的酶活性释放：“小分子”笼形蛋白类似物。
Light-mediated liberation of enzymatic activity: "small molecule" caged protein equivalents.
作者信息
Li Haishan, Hah Jung-Mi, Lawrence David S
机构信息
Department of Biochemistry, The Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, New York 10461, USA.
出版信息
J Am Chem Soc. 2008 Aug 13;130(32):10474-5. doi: 10.1021/ja803395d. Epub 2008 Jul 19.
Abstract
Light-activatable ("caged") proteins have been used to correlate, with exquisite temporal and spatial control, intracellular biochemical action with global cellular behavior. However, the chemical or genetic construction of caged proteins is nontrivial, with subsequent laborious introduction into living cells, potentially problematic competition with natural endogenous counterparts, and challenging intracellular incorporation at levels equivalent to the natural enzymes. We describe the design, synthesis, and characterization of small molecular equivalents of a caged Src kinase. These compounds are easy to prepare and function by inhibiting the action of the natural unmodified enzyme.
摘要
光可激活（“笼化”）蛋白已被用于在精确的时间和空间控制下，将细胞内生化作用与整体细胞行为相关联。然而，笼化蛋白的化学或基因构建并非易事，随后将其费力地导入活细胞中，可能会与天然内源性对应物产生有问题的竞争，并且在与天然酶相当的水平上进行细胞内掺入也具有挑战性。我们描述了一种笼化Src激酶的小分子类似物的设计、合成和表征。这些化合物易于制备，并且通过抑制天然未修饰酶的作用来发挥功能。
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本文引用的文献
1
Light-regulated sampling of protein tyrosine kinase activity.蛋白质酪氨酸激酶活性的光调节采样
J Am Chem Soc. 2006 Nov 1;128(43):14016-7. doi: 10.1021/ja065852z.
2
Acquisition of a "Group A"-selective Src kinase inhibitor via a global targeting strategy.通过全局靶向策略获得一种“A组”选择性Src激酶抑制剂。
J Am Chem Soc. 2006 May 10;128(18):5996-7. doi: 10.1021/ja060136i.
3
Self-reporting fluorescent substrates of protein tyrosine kinases.蛋白质酪氨酸激酶的自报告荧光底物。
J Am Chem Soc. 2006 Feb 15;128(6):1808-9. doi: 10.1021/ja0577692.
4
Adding amino acids to the genetic repertoire.向基因库中添加氨基酸。
Curr Opin Chem Biol. 2005 Dec;9(6):548-54. doi: 10.1016/j.cbpa.2005.10.011. Epub 2005 Nov 2.
5
The preparation and in vivo applications of caged peptides and proteins.笼蔽肽和蛋白质的制备及其体内应用
Curr Opin Chem Biol. 2005 Dec;9(6):570-5. doi: 10.1016/j.cbpa.2005.09.002. Epub 2005 Sep 22.
6
Cofilin promotes actin polymerization and defines the direction of cell motility.丝切蛋白促进肌动蛋白聚合，并确定细胞运动的方向。
Science. 2004 Apr 30;304(5671):743-6. doi: 10.1126/science.1094561.
7
Preparation and light-directed activation of caged proteins.笼锁蛋白的制备与光控激活
Methods Enzymol. 2003;360:274-88. doi: 10.1016/s0076-6879(03)60115-1.
8
Caging proteins through unnatural amino acid mutagenesis.通过非天然氨基酸诱变将蛋白质固定化。
Methods Enzymol. 2003;360:258-73. doi: 10.1016/s0076-6879(03)60114-x.
9
Catalytic subunit of protein kinase A caged at the activating phosphothreonine.蛋白激酶A的催化亚基在激活的磷酸苏氨酸处被笼化。
J Am Chem Soc. 2002 Jul 17;124(28):8220-9. doi: 10.1021/ja020405e.
10
Acquisition of high-affinity, SH2-targeted ligands via a spatially focused library.通过空间聚焦文库获得高亲和力的、靶向SH2的配体。
J Med Chem. 1999 Mar 11;42(5):784-7. doi: 10.1021/jm980663f.
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