Synthesis of a chondroitin sulfate disaccharide library and a GAG-binding protein interaction analysis

Wakao, Masahiro; Obata, Rumi; Miyachi, Kento; Kaitsubata, Yuhei; Kondo, Takao; Sakami, Chiho; Suda, Yasuo

doi:10.1016/j.bmcl.2015.02.054

Cited by 25 publications

(18 citation statements)

References 22 publications

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“…Moreover, the interaction with FGF-2 requires the appropriate sequence of CS tetrasaccharides with such a mixed compositionthe location of the monosulfated disaccharide at the reducing end of such an oligo leads to the binding being voided [123]. On the other hand, both this study [123] and others [104,124,125] revealed a low affinity or a low binding capacity of the 4-O-sulfated disaccharide and the semi-synthetic CSs that contained this disaccharide for some ligands. This property may result from the high conformational rigidity of the 4-O-sulfated CS disaccharide.…”

Section: Monosulfated Disaccharides Provide Interaction Surfaces For mentioning

confidence: 69%

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

et al. 2019

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The remarkable structural heterogeneity of chondroitin sulfate (CS) and dermatan sulfate (DS) generates biological information that can be unique to each of these glycosaminoglycans (GAGs), and changes in their composition are translated into alterations in the binding profiles of these molecules. CS/DS can bind to various cytokines and growth factors, cell surface receptors, adhesion molecules, enzymes and fibrillar glycoproteins of the extracellular matrix, thereby influencing both cell behavior and the biomechanical and biochemical properties of the matrix. In this review, we summarize the current knowledge concerning CS/DS metabolism in the human cancer stroma. The remodeling of the GAG profile in the tumor niche is manifested as a substantial increase in the CS content and a gradual decrease in the proportion between DS and CS. Furthermore, the composition of CS and DS is also affected, which results in a substantial increase in the 6‐O‐sulfated and/or unsulfated disaccharide content, which is concomitant with a decrease in the 4‐O‐sulfation level. Here, we discuss the possible impact of alterations in the CS/DS sulfation pattern on the binding capacity and specificity of these GAGs. Moreover, we propose potential consequences of the stromal accumulation of chondroitin‐6‐sulfate for the progression and metastasis of cancer.

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Section: Monosulfated Disaccharides Provide Interaction Surfaces For mentioning

confidence: 69%

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

et al. 2019

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“…Furthermore, the polymerization of the various disaccharides necessitates stereo-specific formation of a-glycosidic and b-glycosidic linkages. Considerable progress, however, has been made, both for HS [110][111][112][113][114][115] and for CS [116][117][118][119][120]. An emerging and powerful approach is the use of chemoenzymatic strategies [120], which are based on knowledge of HS biosynthesis [104] and HS biosynthetic enzymes [122][123][124].…”

Section: The Structures Recognized By Chemokinesmentioning

confidence: 99%

The sweet spot: how GAGs help chemokines guide migrating cells

Monneau

Arenzana-Seisdedos

Lortat‐Jacob

2015

Journal of Leukocyte Biology

115

113

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Glycosaminoglycans are polysaccharides that occur both at the cell surface and within extracellular matrices. Through their ability to bind to a large array of proteins, almost 500 of which have been identified to date, including most chemokines, these molecules regulate key biologic processes at the cell-tissue interface. To do so, glycosaminoglycans can provide scaffolds to ensure that proteins mediating specific functions will be presented at the correct site and time and can also directly contribute to biologic activities or signaling processes. The binding of chemokines to glycosaminoglycans, which, at the biochemical level, has been mostly studied using heparin, has traditionally been thought of as a mechanism for maintaining haptotactic gradients within tissues along which cells can migrate directionally. Many aspects of chemokine-glycosaminoglycan interactions, however, also suggest that the formation of these complexes could serve additional purposes that go well beyond a simple immobilization process. In addition, progress in glycobiology has revealed that glycosaminoglycan structures, in term of length, sulfation, and epimerization pattern, are specific for cell, tissue, and developmental stage. Glycosaminoglycan regulation and glycosaminoglycan diversity, which cannot be replicated using heparin, thus suggests that these molecules may fine-tune the immune response by selectively recruiting specific chemokines to cell surfaces. In this context, the aim of the present text is to review the chemokine-glycosaminoglycan complexes described to date and provide a critical analysis of the tools, molecules, and strategies that can be used to structurally and functionally investigate the formation of these complexes.

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“…The KEGG pathway hsa00531 describes the glycosaminoglycan degradation biological process. This process is associated with drugs such as chondroitin sulfate, elosulfase alfa and nadroparin [68–70]. Chondroitin sulfate reduces the fat in the blood stream [71, 72].…”

Section: Resultsmentioning

confidence: 99%

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

et al. 2016

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A drug’s biological half-life is defined as the time required for the human body to metabolize or eliminate 50% of the initial drug dosage. Correctly measuring the half-life of a given drug is helpful for the safe and accurate usage of the drug. In this study, we investigated which gene ontology (GO) terms and biological pathways were highly related to the determination of drug half-life. The investigated drugs, with known half-lives, were analyzed based on their enrichment scores for associated GO terms and KEGG pathways. These scores indicate which GO terms or KEGG pathways the drug targets. The feature selection method, minimum redundancy maximum relevance, was used to analyze these GO terms and KEGG pathways and to identify important GO terms and pathways, such as sodium-independent organic anion transmembrane transporter activity (GO:0015347), monoamine transmembrane transporter activity (GO:0008504), negative regulation of synaptic transmission (GO:0050805), neuroactive ligand-receptor interaction (hsa04080), serotonergic synapse (hsa04726), and linoleic acid metabolism (hsa00591), among others. This analysis confirmed our results and may show evidence for a new method in studying drug half-lives and building effective computational methods for the prediction of drug half-lives.

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Synthesis of a chondroitin sulfate disaccharide library and a GAG-binding protein interaction analysis

Cited by 25 publications

References 22 publications

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

The dual role of the glycosaminoglycan chondroitin‐6‐sulfate in the development, progression and metastasis of cancer

The sweet spot: how GAGs help chemokines guide migrating cells

The Use of Gene Ontology Term and KEGG Pathway Enrichment for Analysis of Drug Half-Life

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