The Impact of Chain Length and Flexibility in the Interaction between Sulfated Alginates and HGF and FGF-2.
Identifieur interne : 001321 ( PubMed/Checkpoint ); précédent : 001320; suivant : 001322The Impact of Chain Length and Flexibility in the Interaction between Sulfated Alginates and HGF and FGF-2.
Auteurs : Ystein Arlov [Norvège] ; Finn L. Aachmann [Norvège] ; Emadoldin Feyzi [Norvège] ; Anders Sundan [Norvège] ; Gudmund Skj K-Br K [Norvège]Source :
- Biomacromolecules [ 1526-4602 ] ; 2015.
Descripteurs français
- KwdFr :
- Acide glucuronique (), Acides hexuroniques (), Acides hexuroniques (pharmacologie), Alginates (), Facteur de croissance des hépatocytes (métabolisme), Facteur de croissance fibroblastique de type 2 (métabolisme), Glycosaminoglycanes (), Humains, Héparitine sulfate (), Lignée cellulaire tumorale, Myélome multiple (traitement médicamenteux), Oligosaccharides (), Oligosaccharides (pharmacologie), Sulfates ().
- MESH :
- métabolisme : Facteur de croissance des hépatocytes, Facteur de croissance fibroblastique de type 2.
- pharmacologie : Acides hexuroniques, Oligosaccharides.
- traitement médicamenteux : Myélome multiple.
- Acide glucuronique, Acides hexuroniques, Alginates, Glycosaminoglycanes, Humains, Héparitine sulfate, Lignée cellulaire tumorale, Oligosaccharides, Sulfates.
English descriptors
- KwdEn :
- Alginates (chemistry), Cell Line, Tumor, Fibroblast Growth Factor 2 (metabolism), Glucuronic Acid (chemistry), Glycosaminoglycans (chemistry), Heparitin Sulfate (chemistry), Hepatocyte Growth Factor (metabolism), Hexuronic Acids (chemistry), Hexuronic Acids (pharmacology), Humans, Multiple Myeloma (drug therapy), Oligosaccharides (chemistry), Oligosaccharides (pharmacology), Sulfates (chemistry).
- MESH :
- chemical , chemistry : Alginates, Glucuronic Acid, Glycosaminoglycans, Heparitin Sulfate, Hexuronic Acids, Oligosaccharides, Sulfates.
- chemical , metabolism : Fibroblast Growth Factor 2, Hepatocyte Growth Factor.
- chemical , pharmacology : Hexuronic Acids, Oligosaccharides.
- drug therapy : Multiple Myeloma.
- Cell Line, Tumor, Humans.
Abstract
Alginate is a promising polysaccharide for use in biomaterials as it is biologically inert. One way to functionalize alginate is by chemical sulfation to emulate sulfated glycosaminoglycans, which interact with a variety of proteins critical for tissue development and homeostasis. In the present work we studied the impact of chain length and flexibility of sulfated alginates for interactions with FGF-2 and HGF. Both growth factors interact with defined sequences of heparan sulfate (HS) at the cell surface or in the extracellular matrix. Whereas FGF-2 interacts with a pentasaccharide sequence containing a critical 2-O-sulfated iduronic acid, HGF has been suggested to require a highly sulfated HS/heparin octasaccharide. Here, oligosaccharides of alternating mannuronic and guluronic acid (MG) were sulfated and assessed by their relative efficacy at releasing growth factor bound to the surface of myeloma cells. 8-mers of sulfated MG (SMG) alginate showed significant HGF release compared to shorter fragments, while the maximum efficacy was achieved at a chain length average of 14 monosaccharides. FGF-2 release required a higher concentration of the SMG fragments, and the 14-mer was less potent compared to an equally sulfated high-molecular weight SMG. Sulfated mannuronan (SM) was subjected to periodate oxidation to increase chain flexibility. To assess the change in flexibility, the persistence length was estimated by SEC-MALLS analysis and the Bohdanecky approach to the worm-like chain model. A high degree of oxidation of SM resulted in approximately twice as potent HGF release compared to the nonoxidized SM alginate. The release of FGF-2 also increased with the degree of oxidation, but to a lower degree compared to that of HGF. It was found that the SM alginates were more efficient at releasing FGF-2 than the SMG alginates, indicating a greater dependence on monosaccharide identity and charge orientation over chain flexibility and charge density.
DOI: 10.1021/acs.biomac.5b01125
PubMed: 26406104
Affiliations:
Links toward previous steps (curation, corpus...)
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pubmed:26406104Le document en format XML
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<front><div type="abstract" xml:lang="en">Alginate is a promising polysaccharide for use in biomaterials as it is biologically inert. One way to functionalize alginate is by chemical sulfation to emulate sulfated glycosaminoglycans, which interact with a variety of proteins critical for tissue development and homeostasis. In the present work we studied the impact of chain length and flexibility of sulfated alginates for interactions with FGF-2 and HGF. Both growth factors interact with defined sequences of heparan sulfate (HS) at the cell surface or in the extracellular matrix. Whereas FGF-2 interacts with a pentasaccharide sequence containing a critical 2-O-sulfated iduronic acid, HGF has been suggested to require a highly sulfated HS/heparin octasaccharide. Here, oligosaccharides of alternating mannuronic and guluronic acid (MG) were sulfated and assessed by their relative efficacy at releasing growth factor bound to the surface of myeloma cells. 8-mers of sulfated MG (SMG) alginate showed significant HGF release compared to shorter fragments, while the maximum efficacy was achieved at a chain length average of 14 monosaccharides. FGF-2 release required a higher concentration of the SMG fragments, and the 14-mer was less potent compared to an equally sulfated high-molecular weight SMG. Sulfated mannuronan (SM) was subjected to periodate oxidation to increase chain flexibility. To assess the change in flexibility, the persistence length was estimated by SEC-MALLS analysis and the Bohdanecky approach to the worm-like chain model. A high degree of oxidation of SM resulted in approximately twice as potent HGF release compared to the nonoxidized SM alginate. The release of FGF-2 also increased with the degree of oxidation, but to a lower degree compared to that of HGF. It was found that the SM alginates were more efficient at releasing FGF-2 than the SMG alginates, indicating a greater dependence on monosaccharide identity and charge orientation over chain flexibility and charge density. </div>
</front>
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<Abstract><AbstractText>Alginate is a promising polysaccharide for use in biomaterials as it is biologically inert. One way to functionalize alginate is by chemical sulfation to emulate sulfated glycosaminoglycans, which interact with a variety of proteins critical for tissue development and homeostasis. In the present work we studied the impact of chain length and flexibility of sulfated alginates for interactions with FGF-2 and HGF. Both growth factors interact with defined sequences of heparan sulfate (HS) at the cell surface or in the extracellular matrix. Whereas FGF-2 interacts with a pentasaccharide sequence containing a critical 2-O-sulfated iduronic acid, HGF has been suggested to require a highly sulfated HS/heparin octasaccharide. Here, oligosaccharides of alternating mannuronic and guluronic acid (MG) were sulfated and assessed by their relative efficacy at releasing growth factor bound to the surface of myeloma cells. 8-mers of sulfated MG (SMG) alginate showed significant HGF release compared to shorter fragments, while the maximum efficacy was achieved at a chain length average of 14 monosaccharides. FGF-2 release required a higher concentration of the SMG fragments, and the 14-mer was less potent compared to an equally sulfated high-molecular weight SMG. Sulfated mannuronan (SM) was subjected to periodate oxidation to increase chain flexibility. To assess the change in flexibility, the persistence length was estimated by SEC-MALLS analysis and the Bohdanecky approach to the worm-like chain model. A high degree of oxidation of SM resulted in approximately twice as potent HGF release compared to the nonoxidized SM alginate. The release of FGF-2 also increased with the degree of oxidation, but to a lower degree compared to that of HGF. It was found that the SM alginates were more efficient at releasing FGF-2 than the SMG alginates, indicating a greater dependence on monosaccharide identity and charge orientation over chain flexibility and charge density. </AbstractText>
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<ForeName>Øystein</ForeName>
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<AffiliationInfo><Affiliation>Department of Hematology, St. Olav University Hospital , Erling Skjalgsons Gate 1, 7030 Trondheim, Norway.</Affiliation>
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<Author ValidYN="Y"><LastName>Sundan</LastName>
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<MeshHeading><DescriptorName UI="D017228" MajorTopicYN="N">Hepatocyte Growth Factor</DescriptorName>
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<MeshHeading><DescriptorName UI="D006603" MajorTopicYN="N">Hexuronic Acids</DescriptorName>
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<MeshHeading><DescriptorName UI="D013431" MajorTopicYN="N">Sulfates</DescriptorName>
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<PubmedData><History><PubMedPubDate PubStatus="entrez"><Year>2015</Year>
<Month>9</Month>
<Day>26</Day>
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<PubMedPubDate PubStatus="medline"><Year>2016</Year>
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<ArticleIdList><ArticleId IdType="pubmed">26406104</ArticleId>
<ArticleId IdType="doi">10.1021/acs.biomac.5b01125</ArticleId>
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<affiliations><list><country><li>Norvège</li>
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<tree><country name="Norvège"><region name="Trøndelag"><name sortKey="Arlov, Ystein" sort="Arlov, Ystein" uniqKey="Arlov " first=" Ystein" last="Arlov"> Ystein Arlov</name>
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<name sortKey="Aachmann, Finn L" sort="Aachmann, Finn L" uniqKey="Aachmann F" first="Finn L" last="Aachmann">Finn L. Aachmann</name>
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