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Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics
Chemical Reviews ( IF 51.4 ) Pub Date : 2018-09-11 00:00:00 , DOI: 10.1021/acs.chemrev.8b00354
Nikos K. Karamanos 1, 2 , Zoi Piperigkou 1, 2 , Achilleas D. Theocharis 1 , Hideto Watanabe 3 , Marco Franchi 4 , Stéphanie Baud 5 , Stéphane Brézillon 6 , Martin Götte 7 , Alberto Passi 8 , Davide Vigetti 8 , Sylvie Ricard-Blum 9 , Ralph D. Sanderson 10 , Thomas Neill 11 , Renato V. Iozzo 11
Affiliation  

The extracellular matrix (ECM) constitutes a highly dynamic three-dimensional structural network comprised of macromolecules, such as proteoglycans/glycosaminoglycans (PGs/GAGs), collagens, laminins, fibronectin, elastin, other glycoproteins and proteinases. In recent years, the field of PGs has expanded rapidly. Due to their high structural complexity and heterogeneity, PGs mediate several homeostatic and pathological processes. PGs consist of a protein core and one or more covalently attached GAG chains, which provide the protein cores with the ability to interact with several proteins. The GAG building blocks of PGs significantly influence the chemical and functional properties of PGs. The primary goal of this comprehensive review is to summarize major achievements and paradigm-shifting discoveries made on the PG/GAG chemistry-biology axis, focusing on structural variability, structure–function relationships, metabolic, molecular, and epigenetic mechanisms underlying their synthesis. Recent insights related to exosome biogenesis, degradation, and cell signaling, their status as diagnostic tools and potential pharmacological targets in diseases as well as current applications in nanotechnology and biotechnology are addressed. Moreover, issues related to docking studies, molecular modeling, GAG/PG interaction networks, and their integration are discussed.

中文翻译:

蛋白聚糖的化学多样性驱动多功能细胞调节和治疗。

细胞外基质(ECM)构成了一个高度动态的三维结构网络,该网络由大分子组成,例如蛋白聚糖/糖胺聚糖(PGs / GAG),胶原蛋白,层粘连蛋白,纤连蛋白,弹性蛋白,其他糖蛋白和蛋白酶。近年来,PG的领域迅速扩展。由于PG的高结构复杂性和异质性,它们介导了几种稳态和病理过程。PG由一个蛋白质核心和一个或多个共价连接的GAG链组成,这些链为蛋白质核心提供了与几种蛋白质相互作用的能力。PG的GAG构建基块显着影响PG的化学和功能特性。这项全面审查的主要目标是总结在PG / GAG化学生物学轴上取得的主要成就和范式转变发现,着重于结构变异性,结构与功能的关系,代谢,分子和表观遗传机制的基础。解决了有关外泌体生物发生,降解和细胞信号转导的最新见解,它们在疾病中的诊断工具地位和潜在药理学目标以及纳米技术和生物技术中的当前应用。此外,还讨论了与对接研究,分子建模,GAG / PG相互作用网络及其集成有关的问题。讨论了它们在疾病中作为诊断工具的地位和潜在的药理学目标,以及在纳米技术和生物技术中的当前应用。此外,还讨论了与对接研究,分子建模,GAG / PG相互作用网络及其集成有关的问题。讨论了它们在疾病中作为诊断工具的地位和潜在的药理学目标,以及在纳米技术和生物技术中的当前应用。此外,还讨论了与对接研究,分子建模,GAG / PG相互作用网络及其集成有关的问题。
更新日期:2018-09-11
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