Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases
► Sulfated LMWLs potently inhibit factor XIa, leukocyte elastase and cathepsin G. ► Sulfated LMWLs do not inhibit factors VIIa, IXa, and XIIa, activated protein C and plasma kallikrein. ► Sulfated LMWLs compete with heparin for binding to factors Xa and XIa. ► The results will aid the design of anti...
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| Veröffentlicht in: | Biochemical and biophysical research communications 2012-01, Vol.417 (1), p.382-386 |
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| creator | Henry, Brian L. Thakkar, Jay N. Liang, Aiye Desai, Umesh R. |
| description | ► Sulfated LMWLs potently inhibit factor XIa, leukocyte elastase and cathepsin G. ► Sulfated LMWLs do not inhibit factors VIIa, IXa, and XIIa, activated protein C and plasma kallikrein. ► Sulfated LMWLs compete with heparin for binding to factors Xa and XIa. ► The results will aid the design of anticoagulants based on the sulfated LMWL scaffold.
Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of low molecular weight heparins (LMWHs), have been found to bind in exosite II of thrombin [12]. To assess whether sulfated LMWLs recognize other heparin-binding proteins, we studied their effect on serine proteases of the coagulation, inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay, sulfated LMWLs were found to potently inhibit coagulation factor XIa and human leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for binding to factors Xa and XIa. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold. |
| doi_str_mv | 10.1016/j.bbrc.2011.11.122 |
| format | Article |
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Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of low molecular weight heparins (LMWHs), have been found to bind in exosite II of thrombin [12]. To assess whether sulfated LMWLs recognize other heparin-binding proteins, we studied their effect on serine proteases of the coagulation, inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay, sulfated LMWLs were found to potently inhibit coagulation factor XIa and human leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for binding to factors Xa and XIa. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold.</description><identifier>ISSN: 0006-291X</identifier><identifier>EISSN: 1090-2104</identifier><identifier>DOI: 10.1016/j.bbrc.2011.11.122</identifier><identifier>PMID: 22155248</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Anticoagulants ; Anticoagulants - chemistry ; Anticoagulants - pharmacology ; Binding, Competitive ; cathepsin G ; chymotrypsin ; Coagulation ; Drug Design ; elastase ; Enzyme inhibition ; heparin ; Heparin - chemistry ; Heparin-binding proteins ; Humans ; hydrolysis ; leukocytes ; lignin ; Lignin - chemistry ; Lignin - pharmacology ; Molecular Mimicry ; Molecular Weight ; plasma kallikrein ; Serine Proteases - chemistry ; Serine Proteinase Inhibitors - chemistry ; Serine Proteinase Inhibitors - pharmacology ; Sulfates - chemistry ; thrombin ; trypsin</subject><ispartof>Biochemical and biophysical research communications, 2012-01, Vol.417 (1), p.382-386</ispartof><rights>2011 Elsevier Inc.</rights><rights>Copyright © 2011 Elsevier Inc. All rights reserved.</rights><rights>2011 Elsevier Inc. All rights reserved. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c487t-76fd2aa1edd7a58f14045c8813c014a001117c1c6812bd28f01b520c084609c53</citedby><cites>FETCH-LOGICAL-c487t-76fd2aa1edd7a58f14045c8813c014a001117c1c6812bd28f01b520c084609c53</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bbrc.2011.11.122$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,777,781,882,3537,27905,27906,45976</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22155248$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Henry, Brian L.</creatorcontrib><creatorcontrib>Thakkar, Jay N.</creatorcontrib><creatorcontrib>Liang, Aiye</creatorcontrib><creatorcontrib>Desai, Umesh R.</creatorcontrib><title>Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases</title><title>Biochemical and biophysical research communications</title><addtitle>Biochem Biophys Res Commun</addtitle><description>► Sulfated LMWLs potently inhibit factor XIa, leukocyte elastase and cathepsin G. ► Sulfated LMWLs do not inhibit factors VIIa, IXa, and XIIa, activated protein C and plasma kallikrein. ► Sulfated LMWLs compete with heparin for binding to factors Xa and XIa. ► The results will aid the design of anticoagulants based on the sulfated LMWL scaffold.
Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of low molecular weight heparins (LMWHs), have been found to bind in exosite II of thrombin [12]. To assess whether sulfated LMWLs recognize other heparin-binding proteins, we studied their effect on serine proteases of the coagulation, inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay, sulfated LMWLs were found to potently inhibit coagulation factor XIa and human leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for binding to factors Xa and XIa. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold.</description><subject>Anticoagulants</subject><subject>Anticoagulants - chemistry</subject><subject>Anticoagulants - pharmacology</subject><subject>Binding, Competitive</subject><subject>cathepsin G</subject><subject>chymotrypsin</subject><subject>Coagulation</subject><subject>Drug Design</subject><subject>elastase</subject><subject>Enzyme inhibition</subject><subject>heparin</subject><subject>Heparin - chemistry</subject><subject>Heparin-binding proteins</subject><subject>Humans</subject><subject>hydrolysis</subject><subject>leukocytes</subject><subject>lignin</subject><subject>Lignin - chemistry</subject><subject>Lignin - pharmacology</subject><subject>Molecular Mimicry</subject><subject>Molecular Weight</subject><subject>plasma kallikrein</subject><subject>Serine Proteases - chemistry</subject><subject>Serine Proteinase Inhibitors - chemistry</subject><subject>Serine Proteinase Inhibitors - pharmacology</subject><subject>Sulfates - chemistry</subject><subject>thrombin</subject><subject>trypsin</subject><issn>0006-291X</issn><issn>1090-2104</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kV1rFTEQhoMo9rT6B7yQ3NkL9zST_cqCCFKsCgUvquBdyCaze3LISdZkt6X_3iynFr0pDIQwz7zz8RLyBtgWGDQX-23fR73lDGC7BufPyAZYxwoOrHpONoyxpuAd_DohpyntWQarpntJTjiHuuaV2BB1s7hBzWjeUxfu6CE41ItTkd6hHXczdXb01idq_c72dqaKJszITMcYlomGge5wUtH6orfeWD_mfP4hnWKYUSVMr8iLQbmErx_eM_Lz6vOPy6_F9fcv3y4_XRe6Eu1ctM1guFKAxrSqFgNUrKq1EFBqBpVaZ4dWg24E8N5wMTDoa840E1XDOl2XZ-TjUXda-gMajX6Oyskp2oOK9zIoK__PeLuTY7iVJa873oos8O5BIIbfC6ZZHmzS6JzyGJYkO2hyQ-BlJs-fJKEty7osBVQZ5UdUx5BSxOFxIGBydVHu5eqiXF2Ua3Cei97-u8pjyV_bMvDhCGA-6K3FKJO26DUaG7M50gT7lP4ft5Gu8g</recordid><startdate>20120106</startdate><enddate>20120106</enddate><creator>Henry, Brian L.</creator><creator>Thakkar, Jay N.</creator><creator>Liang, Aiye</creator><creator>Desai, Umesh R.</creator><general>Elsevier Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7S9</scope><scope>L.6</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20120106</creationdate><title>Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases</title><author>Henry, Brian L. ; Thakkar, Jay N. ; Liang, Aiye ; Desai, Umesh R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c487t-76fd2aa1edd7a58f14045c8813c014a001117c1c6812bd28f01b520c084609c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Anticoagulants</topic><topic>Anticoagulants - chemistry</topic><topic>Anticoagulants - pharmacology</topic><topic>Binding, Competitive</topic><topic>cathepsin G</topic><topic>chymotrypsin</topic><topic>Coagulation</topic><topic>Drug Design</topic><topic>elastase</topic><topic>Enzyme inhibition</topic><topic>heparin</topic><topic>Heparin - chemistry</topic><topic>Heparin-binding proteins</topic><topic>Humans</topic><topic>hydrolysis</topic><topic>leukocytes</topic><topic>lignin</topic><topic>Lignin - chemistry</topic><topic>Lignin - pharmacology</topic><topic>Molecular Mimicry</topic><topic>Molecular Weight</topic><topic>plasma kallikrein</topic><topic>Serine Proteases - chemistry</topic><topic>Serine Proteinase Inhibitors - chemistry</topic><topic>Serine Proteinase Inhibitors - pharmacology</topic><topic>Sulfates - chemistry</topic><topic>thrombin</topic><topic>trypsin</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Henry, Brian L.</creatorcontrib><creatorcontrib>Thakkar, Jay N.</creatorcontrib><creatorcontrib>Liang, Aiye</creatorcontrib><creatorcontrib>Desai, Umesh R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Biochemical and biophysical research communications</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Henry, Brian L.</au><au>Thakkar, Jay N.</au><au>Liang, Aiye</au><au>Desai, Umesh R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases</atitle><jtitle>Biochemical and biophysical research communications</jtitle><addtitle>Biochem Biophys Res Commun</addtitle><date>2012-01-06</date><risdate>2012</risdate><volume>417</volume><issue>1</issue><spage>382</spage><epage>386</epage><pages>382-386</pages><issn>0006-291X</issn><eissn>1090-2104</eissn><abstract>► Sulfated LMWLs potently inhibit factor XIa, leukocyte elastase and cathepsin G. ► Sulfated LMWLs do not inhibit factors VIIa, IXa, and XIIa, activated protein C and plasma kallikrein. ► Sulfated LMWLs compete with heparin for binding to factors Xa and XIa. ► The results will aid the design of anticoagulants based on the sulfated LMWL scaffold.
Sulfated low molecular weight lignins (LMWLs), designed as oligomeric mimetics of low molecular weight heparins (LMWHs), have been found to bind in exosite II of thrombin [12]. To assess whether sulfated LMWLs recognize other heparin-binding proteins, we studied their effect on serine proteases of the coagulation, inflammatory and digestive systems. Using chromogenic substrate hydrolysis assay, sulfated LMWLs were found to potently inhibit coagulation factor XIa and human leukocyte elastase, moderately inhibit cathepsin G and not inhibit coagulation factors VIIa, IXa, and XIIa, plasma kallikrein, activated protein C, trypsin, and chymotrypsin. Competition studies show that UFH competes with sulfated LMWLs for binding to factors Xa and XIa. These results further advance the concept of sulfated LMWLs as heparin mimics and will aid the design of anticoagulants based on their novel scaffold.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>22155248</pmid><doi>10.1016/j.bbrc.2011.11.122</doi><tpages>5</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Anticoagulants Anticoagulants - chemistry Anticoagulants - pharmacology Binding, Competitive cathepsin G chymotrypsin Coagulation Drug Design elastase Enzyme inhibition heparin Heparin - chemistry Heparin-binding proteins Humans hydrolysis leukocytes lignin Lignin - chemistry Lignin - pharmacology Molecular Mimicry Molecular Weight plasma kallikrein Serine Proteases - chemistry Serine Proteinase Inhibitors - chemistry Serine Proteinase Inhibitors - pharmacology Sulfates - chemistry thrombin trypsin |
| title | Sulfated, low molecular weight lignins inhibit a select group of heparin-binding serine proteases |
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