Heparin-derived heparan sulfate mimics to modulate heparan sulfate-protein interaction in inflammation and cancer.
Heparin-derived heparan sulfate mimics to modulate heparan sulfate-protein interaction in inflammation and cancer.
复制标题
DOI：
10.1016/j.matbio.2010.04.003
复制
发表时间：
2010-07
期刊：
影响因子：
6.9
通讯作者：
Torri, Giangiacomo
中科院分区：
文献类型：
--
作者：
Casu, Benito;Naggi, Annamaria;Torri, Giangiacomo
关键词：
硫酸乙酰肝素蛋白聚糖（HSPG）的硫酸乙酰肝素（HS）链是细胞表面和细胞外基质（EC）的"普遍存在的"组分，并且在发育和稳态过程的生理病理学中起重要作用。HS的大多数生物学性质是通过与"肝素结合蛋白"的相互作用介导的，并且可以通过外源性肝素种类（未修饰的肝素、低分子量肝素、较短的肝素寡糖和不同大小的各种非抗凝剂衍生物）来调节。肝素物质可以在不同程度上促进或抑制HS活性，这取决于它们的结构与生物活性HS序列的相似程度。肝素与HS具有结构相似性，但富含"完全硫酸化"序列（S结构域），这些序列通常是肝素/HS结合蛋白的最强结合剂。另一方面，HS通常富含较少硫酸化的N-乙酰化序列（NA结构域）。HS链的某些功能，例如通过促进蛋白质的二聚化来激活蛋白质的功能，通常需要由相当长的NA序列分隔的短S序列。这些物质的生物活性不能被肝素模拟，除非这种多糖经过适当的化学/酶改性或生物技术改造。这个小审查涵盖了一些信息和概念的相互作用的HS链与肝素结合蛋白和一些方法调节HS相互作用相关的炎症和癌症。这是接近通过几个说明性的例子，包括HS和肝素衍生的物种与趋化因子IL-8，生长因子FGF1和FGF2的相互作用，和这些物种的乙酰肝素酶的活性的调制。HS链测序和通过化学合成或半合成复制它们的进展，以及寡糖-蛋白质复合物的3D结构的阐明，为在炎症和癌症领域以及其他治疗领域开发HS启发药物的合理方法铺平了道路。
The heparan sulfate (HS) chains of heparan sulfate proteoglycans (HSPG) are “ubiquitous” components of the cell surface and the extracellular matrix (EC) and play important roles in the physiopathology of developmental and homeostatic processes. Most biological properties of HS are mediated by interactions with “heparin-binding proteins” and can be modulated by exogenous heparin species (unmodified heparin, low molecular weight heparins, shorter heparin oligosaccharides and various non-anticoagulant derivatives of different sizes). Heparin species can promote or inhibit HS activities to different extents depending, among other factors, on how closely their structure mimics the biologically active HS sequences. Heparin shares structural similarities with HS, but is richer in “fully sulfated” sequences (S domains) that are usually the strongest binders to heparin/HS-binding proteins. On the other hand, HS is usually richer in less sulfated, N-acetylated sequences (NA domains). Some of the functions of HS chains, such as that of activating proteins by favoring their dimerization, often require short S sequences separated by rather long NA sequences. The biological activities of these species cannot be simulated by heparin, unless this polysaccharide is appropriately chemically/enzymatically modified or biotechnologically engineered. This mini review covers some information and concepts concerning the interactions of HS chains with heparin-binding proteins and some of the approaches for modulating HS interactions relevant to inflammation and cancer. This is approached through a few illustrative examples, including the interaction of HS and heparin-derived species with the chemokine IL-8, the growth factors FGF1 and FGF2, and the modulation of the activity of the enzyme heparanase by these species. Progresses in sequencing HS chains and reproducing them either by chemical synthesis or semi-synthesis, and in the elucidation of the 3D structure of oligosaccharide–protein complexes, are paving the way for rational approaches to the development of HS-inspired drugs in the field of inflammation and cancer, as well in other therapeutic fields.
登录
查看更多内容
DOI：
10.1016/j.bbagen.2008.09.001
发表时间：
2009-01-01
影响因子：
3
作者：
Asada, Masahiro;Shinomiya, Michiyo;Imamura, Toru
通讯作者：
Imamura, Toru
影响因子：
4
作者：
de Paz, Lose L.;Moseman, E. Ashley;Seeberger, Peter H.
通讯作者：
Seeberger, Peter H.
影响因子：
--
作者：
Casu B;Vlodavsky I;Sanderson RD
通讯作者：
Sanderson RD
影响因子：
15
作者：
Arungundram, Sailaja;Al-Mafraji, Kanar;Asong, Jinkeng;Leach, Franklin E., III;Amster, I. Jonathan;Venot, Andre;Turnbull, Jeremy E.;Boons, Geert-Jan
通讯作者：
Boons, Geert-Jan
DOI：
10.1590/s0001-37652009000300007
发表时间：
2009-09-01
期刊：
Anais da Academia Brasileira de Ciências
影响因子：
--
作者：
Dreyfuss, Juliana L.;Regatieri, Caio V.;Nader, Helena B.
通讯作者：
Nader, Helena B.