Synthesis and mammalian cell compatibility of light-released glycan precursors for controlled metabolic engineering.
Synthesis and mammalian cell compatibility of light-released glycan precursors for controlled metabolic engineering.
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DOI：
10.1016/j.bmc.2022.116918
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发表时间：
2022-09-15
影响因子：
3.5
通讯作者：
Fehl, Charlie
中科院分区：
文献类型：
--
作者：
Kondor, Courtney A.;Gorantla, Jaggaiah N.;Leonard, Garry D.;Fehl, Charlie
关键词：
糖添加到生物分子或聚糖中是生物学中最丰富的生物分子修饰，因为它们使细胞能够适应不断变化的营养和压力条件。糖生物学领域的一个未解决的挑战是研究具有化学控制的聚糖生物合成途径，特别是在活细胞环境中。本研究的目的是创建具有控释特性的生物相容性聚糖前体。在这里，我们报告11个“笼”糖探针，释放聚糖生物合成前体分子曝光后。我们用探针靶向的特定糖通路调节N-乙酰基糖GlcNAc、GalNAc和唾液酸添加到细胞中的生物分子上，其中每一种都有可能改变涉及细胞形态、信号传导和行为的聚糖过程。我们假设我们的聚糖前体探针将保持生物惰性，直到满足光引发的脱老化条件，避免生物活性，包括代谢和细胞毒性。光笼化的GlcNAc、GalNAc和ManNAc（唾液酸前体）糖类似物，我们称之为“光糖”，在其最佳波长下曝光数分钟内释放。在研究过程中，我们表征了这些糖在其各自的脱笼条件下的细胞相容性，并发现了高度细胞相容的GlcNAc、GalNAc和ManNAc光笼前体。GlcNAc-1-磷酸前体的释放导致细胞中ATP水平的改变，证明了初步的代谢工程。我们设想这些探针作为有用的补充，化学糖生物学领域，将使时空控制在活的哺乳动物细胞中的糖基化途径。
Sugar additions to biomolecules, or glycans, are some of the most abundant biomolecule modifications in biology because they enable cells to adapt to changing nutrient and stress conditions. An unmet challenge for the field of glycobiology is the study of glycan biosynthetic pathways with chemical control, especially in live cell settings. The objective of this study was to create biocompatible glycan precursors with controlled release properties. Here, we report eleven “caged” sugar probes that release glycan biosynthetic precursor molecules upon light exposure. The specific sugar pathways we target with our probes regulate the addition of the N-acetyl sugars GlcNAc, GalNAc, and sialic acid onto biomolecules in cells, each of which has the potential to alter glycan processes involved in cell morphology, signaling, and behavior. We hypothesized that our glycan precursor probes would remain biologically inert until light-initiated decaging conditions were met, avoiding biological activities including metabolism and cytotoxicity. The photocaged analogs of GlcNAc, GalNAc, and ManNAc (sialic acid precursor) sugars, which we call “photo-sugars,” were released within minutes of light exposure at their optimal wavelengths. During the course of the study, we characterized the cell compatibility of these sugars under their respective decaging conditions, and found highly cell compatible GlcNAc, GalNAc, and ManNAc photocaged precursors. Release of GlcNAc-1-phosphate precursors led to altered ATP levels in cells, demonstrating preliminary metabolic engineering. We envision these probes as useful additions to the chemical glycobiology field that will enable spatiotemporal control over glycosylation pathways in living mammalian cells.
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影响因子：
16.6
作者：
Chang, Pamela V.;Chen, Xing;Smyrniotis, Chris;Xenakis, Alexander;Hu, Tianshun;Bertozzi, Carolyn R.;Wu, Peng
通讯作者：
Wu, Peng
影响因子：
4.3
作者：
Ma, Junfeng;Li, Yaoxiang;Wu, Ci
通讯作者：
Wu, Ci
DOI：
10.1083/jcb.201501101
发表时间：
2015-03-30
期刊：
The Journal of cell biology
影响因子：
--
作者：
Bond MR;Hanover JA
通讯作者：
Hanover JA
影响因子：
4.8
作者：
Kreppel, LK;Hart, GW
通讯作者：
Hart, GW
影响因子：
5.4
作者：
Cheng, Bo;Wan, Yi;Chen, Xing
通讯作者：
Chen, Xing