揭示化硫酸肝素模仿剂和信号蛋白之间的结构功能相互作用
Virendrasinh Mahida1, Rakesh Raigawali1, Paula González2
1Department of Chemistry, Indian Institute of Science Education and Research Pune 411008 India rkikkeri@iiserpune.ac.in.
RSC chemical biology
|August 4, 2025
概括
化碳水化合物为研究蛋白质结合和开发药物提供了新的途径. 合成的硫酸肝素模仿剂与显示保留了结合性质,为新疗法铺平了道路.
科学领域:
- 葡萄糖生物学 葡萄糖生物学
- 药用化学 医学化学
- 碳水化合物化学 碳水化合物化学
背景情况:
- 化碳水化合物是糖生物学的宝贵工具.
- 它们有助于阐明基团在蛋白质结合和药物发现中的作用.
研究的目的:
- 为了合成肝硫酸 (HS) 模仿剂与在葡萄糖酸残留物的C3位置.
- 调节结构-功能关系并评估结合性质.
主要方法:
- 不同的合成策略. 不同的合成策略.
- 19F-NMR光谱学,JHH合,以及NOE数据分析.
- 糖甘微阵列和SPR结合研究.
主要成果:
- 合成了7种HS模仿剂与C3化葡萄糖酸.
- 替代证实了对硫化模式的敏感性,并保留了葡萄糖酸构型.
- HS模拟剂保留了N-乙化HS序列对生长因子和化学因子的结合.
- 特定的化模拟剂的结合性与高N硫酸原生HS配体相比较.
结论:
- 在HS模拟剂中用基替代基是一种可行的策略,可以调节结构功能关系.
- 这些发现支持开发针对形态原体和细胞信号通路的新型治疗剂.
相关概念视频
Assembly of Signaling Complexes
5.9K
Multiprotein signaling complexes are formed in a dynamic process involving protein-protein interactions at the cytoplasmic domain of transmembrane receptors or enzymatic and non-enzymatic proteins associated with the receptor. These complexes ensure the activation and propagation of intracellular signals that regulate cell functions.
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
Interaction domains in cell signaling
Interaction domains recognize exposed features of their binding partners containing post-translationally modified sequences,...
5.9K
Amplifying Signals via Enzymatic Cascade
8.8K
When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze...
8.8K
Intracellular Signaling Affects Focal Adhesions
2.8K
Integrins act both as extracellular input receivers and as intracellular processing activators. As their name suggests, integrins are entirely integrated into the membrane structure. Their hydrophobic membrane-spanning regions interact with the phospholipid bilayer's hydrophobic region. These membrane receptors provide extracellular attachment sites for effectors like hormones and growth factors. They activate intracellular response cascades when their effectors are bound and active.
Some...
Some...
2.8K
Interactions Between Signaling Pathways
6.4K
Signaling cascades usually lack linearity. Multiple pathways interact and regulate one another, allowing cells to integrate and respond to diverse environmental stimuli.
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
Convergence and divergence, and cross-talk between signaling pathways
Two distinct signaling pathways can converge on a single functional unit, which may either be a single protein or a complex of proteins. The response is either functionally distinct or synergistic between the two pathways but different from the response...
6.4K
The JAK-STAT Signaling Pathway
9.2K
Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as SH2...
9.2K
Chemical Signaling in the Endocrine System
3.9K
A signaling cascade is a series of events that facilitates the transmission of information within or between cells, culminating in a targeted response in the recipient cell. As chemical messengers, hormones are pivotal in initiating and modulating these intricate signaling cascades based on their solubility.
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...
Lipid-soluble hormones, such as steroid hormones, demonstrate an intracellular action. These hormones traverse cell membranes due to their lipid nature. Once inside the target cell, they...
3.9K


