دانلود رایگان مقاله لاتین ویژگی ساختاری hpse از سایت الزویر
عنوان فارسی مقاله:
ویژگی های ساختاری HPSE - مهار هپارین غیر ضد انعقاد مشتق Roneparstat
عنوان انگلیسی مقاله:
Structural features of heparanase-inhibiting non-anticoagulant heparin derivative Roneparstat
سال انتشار : 2016
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مقدمه انگلیسی مقاله:
1. Introduction
Heparanase, an endoglycosidase confined inside specific cells under normal conditions, is overexpressed in most human oncological diseases, promoting tumor metastasis and angiogenesis (Pisano, Vlodavsky, Ilan, & Zunino, 2014; Vlodavsky & Friedman, 2001). The mechanism of its action under pathological conditions is believed to be associated with the release of physiologically and pathologically important molecules (growth factors, cytokines, chemokines and other proteins). Their release is facilitated in tumors by heparanase, degrading heparan sulfate (HS) chains of HS proteoglycans on cell surfaces and within the extracellular matrix (ECM) (Vlodavsky & Friedman, 2001). HS/heparanase interactions have generated interest as target for anti-cancer therapy. The crystal structure of heparanase, recently published, is expected to further stimulate interest in the investigation and design of its inhibitors (Wu, Viola, Brzozowski, & Davies, 2015). Among current approaches used for heparanase inhibition (Ferro et al., 2007; Ferro et al., 2012), development of heparin derivatives, e.g.glycolsplit (gs) heparins (Mousa, Linhardt, Francis, & Amirkhosravi, 2006; Ritchie et al., 2011) as HS mimics, is of considerable interest. Heparin is a polydisperse, linear, highly sulfated glucosaminoglycan (GAG), consisting of uronic acid − glucosamine repeating disaccharide building blocks with different sulfation and acetylation degrees, which vary in heparins of different origin. In spite of these variations, some structural features are considered common to heparins from all sources (Casu & Lindahl, 2001; Fu et al., 2013; Yates et al., 1996; Zhang et al., 2011). The trisulfated disaccharide ANS6S − I2S (N-sulfated d-glucosamine-6-O-sulfate − 2-O-sulfated l-iduronic acid) is the prevalent building block present within highly sulfated regions (Casu, 2005), while the disaccharide ANAc − G (N-acetyl-d-glucosamine − d-glucuronic acid) is the main constituent of the undersulfated sequences of heparin (Yamada, Yamane, Tsuda, Yoshida, & Sugahara, 1998). d-Glucuronic acid followed by a trisulfated glucosamine ANS3S6S (N-sulfated dglucosamine-3,6-O-disulfate), formed at the last biosynthesis step within some heparin chains, is the marker of the pentasaccharide sequence ANAc6S-G-ANS3S6S-I2S-ANS6S and its variants (Loganathan, Wang,Mallis, & Linhardt, 1990; Naggi et al., 2016). These sequences, interacting with antithrombin, largely determine the anticoagulant activity of heparin. A linkage region (LR) G-(Gal)2-Xyl-Ser tetrasaccharide can be also present atthe reducing end (RE) of some heparin chains (Iacomini et al., 1999). This particular sequence, susceptible to treatments used during industrial heparin API preparation, usually varies within the range 1.0–1.3% (Zhang et al., 2011). These and other minor constituents give rise to the structural microheterogeneity of heparin and may contribute to the wide variety of interactions with different biomolecules (Shriver, Capila, Venkataraman, & Sasisekharan, 2012). At the same time, such variety significantly complicates structural characterization of heparin-related compounds.
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کلمات کلیدی:
Investigating Glycol-Split-Heparin-Derived Inhibitors of Heparanase: A ... www.mdpi.com/1420-3049/21/11/1602/pdf by M Ni - 2016 - Related articles Nov 23, 2016 - and necuparanib, heparanase inhibitors obtained from heparin and ...... A. Structural features of heparanase-inhibiting non-anticoagulant. Encyclopedia of Cancer - Page 1338 - Google Books Result https://books.google.com/books?isbn=3540368477 Manfred Schwab - 2008 - Medical Expression of HS degrading heparanase correlates with the metastatic ... Apart of the well studied catalytic feature of the enzyme, heparanase was noted to exert ... Clinical Relevance Heparanase inhibiting molecules (e. g., non-anticoagulant ... Tumor Angiogenesis: Basic Mechanisms and Cancer Therapy https://books.google.com/books?isbn=3540331778 Dieter Marmé, Norbert Fusenig - 2007 - Medical ... identification of some of its structural features associated with inhibition of the enzyme. We have analyzed the heparanase-inhibiting effect of heparin derivatives ... N-acetylation, and glycol splitting of non-sulfated uronic acid residues (Naggi et al. ... Moreover, glycol- splitting involves substantial loss of the anticoagulant ... Antitumor properties of a new non-anticoagulant heparin analog from ... https://academic.oup.com/glycob/.../Antitumor-properties-of-a-new-non-anticoagulant by AM Gomes - 2015 - Cited by 9 - Related articles Nov 3, 2014 - Antitumor properties of a new non-anticoagulant heparin analog from .... The mollusk glycan also inhibits heparanase enzymatic activity in vitro. Non-Anticoagulant Heparins and Inhibition of Cancer www.karger.com/Article/PDF/175157 by B Casu - 2007 - Cited by 127 - Related articles factors, heparanase, and selectins by heparin derivatives are somewhat different for ... tion of a non-anticoagulant heparin that inhibits cancer in animal models without ... features associated with its potent anticoagulant activity. The emerging ... Lysosomes: Biology, Diseases, and Therapeutics https://books.google.com/books?isbn=1118645154 Frederick R. Maxfield, James M. Willard, Shuyan Lu - 2016 - Medical However, it is not clinically usable due to its potent anticoagulant ... The PI-88, a heparanase inhibitor with potent antiangiogenicactivity ... 10.4.1.5 Sialidase 1/Neuraminidase 1 Aberrant glycosylation is one of the typical features of cancer cells ...
