Novel Anticoagulant Peptide from Lactoferrin Binding Thrombin at the Active Site and Exosite‑I
Thrombin is currently one of the important targets for the treatment and prevention of thrombosis. At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was...
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| Veröffentlicht in: | Journal of agricultural and food chemistry 2020-03, Vol.68 (10), p.3132-3139 |
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| creator | Xu, Shiqi Fan, Fengjiao Liu, Hanxiong Cheng, Shuzhen Tu, Maolin Du, Ming |
| description | Thrombin is currently one of the important targets for the treatment and prevention of thrombosis. At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was shown to possess antithrombotic activity. LF-LR (5 mM) significantly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time for 13.4, 1.7, and 5.1 s, respectively. It prolonged the coagulation time of fibrinogen from 15.3 ± 0.4 to 20.2 ± 0.5 s by affecting the conformation of thrombin. Using circular dichroism analysis, LF-LR can increase the α-helix content of thrombin from 25.6 to 56.7% and made the β-sheet disappear. In addition, LF-LR also quenched fluorescence of thrombin at about 346 nm (λEx = 280 nm). By means of molecular docking, it was found that LF-LR could bind to both the active site and the exosite-I of thrombin, and the combined LYS60F, TRP60D, ASP189, LYS36, and ARG77A are typical amino acids in the two domains, respectively. |
| doi_str_mv | 10.1021/acs.jafc.9b08094 |
| format | Article |
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At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was shown to possess antithrombotic activity. LF-LR (5 mM) significantly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time for 13.4, 1.7, and 5.1 s, respectively. It prolonged the coagulation time of fibrinogen from 15.3 ± 0.4 to 20.2 ± 0.5 s by affecting the conformation of thrombin. Using circular dichroism analysis, LF-LR can increase the α-helix content of thrombin from 25.6 to 56.7% and made the β-sheet disappear. In addition, LF-LR also quenched fluorescence of thrombin at about 346 nm (λEx = 280 nm). By means of molecular docking, it was found that LF-LR could bind to both the active site and the exosite-I of thrombin, and the combined LYS60F, TRP60D, ASP189, LYS36, and ARG77A are typical amino acids in the two domains, respectively.</description><identifier>ISSN: 0021-8561</identifier><identifier>EISSN: 1520-5118</identifier><identifier>DOI: 10.1021/acs.jafc.9b08094</identifier><identifier>PMID: 32064873</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amino Acid Sequence ; Animals ; Anticoagulants - chemistry ; Binding Sites ; Catalytic Domain ; Cattle ; Fibrinogen - chemistry ; Humans ; Kinetics ; Lactoferrin - chemistry ; Molecular Docking Simulation ; Peptides - chemistry ; Protein Binding ; Thrombin - chemistry ; Thrombin Time</subject><ispartof>Journal of agricultural and food chemistry, 2020-03, Vol.68 (10), p.3132-3139</ispartof><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a336t-3585cdee278ffda1b8e0ee99856b6f03296b33cf6cbf5540a081d3579abf852e3</citedby><cites>FETCH-LOGICAL-a336t-3585cdee278ffda1b8e0ee99856b6f03296b33cf6cbf5540a081d3579abf852e3</cites><orcidid>0000-0001-5872-8529</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/acs.jafc.9b08094$$EPDF$$P50$$Gacs$$H</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/acs.jafc.9b08094$$EHTML$$P50$$Gacs$$H</linktohtml><link.rule.ids>314,780,784,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32064873$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Xu, Shiqi</creatorcontrib><creatorcontrib>Fan, Fengjiao</creatorcontrib><creatorcontrib>Liu, Hanxiong</creatorcontrib><creatorcontrib>Cheng, Shuzhen</creatorcontrib><creatorcontrib>Tu, Maolin</creatorcontrib><creatorcontrib>Du, Ming</creatorcontrib><title>Novel Anticoagulant Peptide from Lactoferrin Binding Thrombin at the Active Site and Exosite‑I</title><title>Journal of agricultural and food chemistry</title><addtitle>J. Agric. Food Chem</addtitle><description>Thrombin is currently one of the important targets for the treatment and prevention of thrombosis. At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was shown to possess antithrombotic activity. LF-LR (5 mM) significantly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time for 13.4, 1.7, and 5.1 s, respectively. It prolonged the coagulation time of fibrinogen from 15.3 ± 0.4 to 20.2 ± 0.5 s by affecting the conformation of thrombin. Using circular dichroism analysis, LF-LR can increase the α-helix content of thrombin from 25.6 to 56.7% and made the β-sheet disappear. In addition, LF-LR also quenched fluorescence of thrombin at about 346 nm (λEx = 280 nm). By means of molecular docking, it was found that LF-LR could bind to both the active site and the exosite-I of thrombin, and the combined LYS60F, TRP60D, ASP189, LYS36, and ARG77A are typical amino acids in the two domains, respectively.</description><subject>Amino Acid Sequence</subject><subject>Animals</subject><subject>Anticoagulants - chemistry</subject><subject>Binding Sites</subject><subject>Catalytic Domain</subject><subject>Cattle</subject><subject>Fibrinogen - chemistry</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Lactoferrin - chemistry</subject><subject>Molecular Docking Simulation</subject><subject>Peptides - chemistry</subject><subject>Protein Binding</subject><subject>Thrombin - chemistry</subject><subject>Thrombin Time</subject><issn>0021-8561</issn><issn>1520-5118</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kMFOGzEURS1URNK0e1bIyy6Y8DweO55lQNAiRYAEXU89nufEKBkH24Porr_QX-RLaprQXVe27HOv3juEHDOYMijZmTZx-qitmdYtKKirAzJmooRCMKY-kDFkplBCshH5GOMjACgxgyMy4iXISs34mPy48c-4pvM-OeP1cljrPtE73CbXIbXBb-hCm-QthuB6eu76zvVL-rDKP21-0ImmFdK5Se4Z6b1LSHXf0csXH_P99dfv60_k0Op1xM_7c0K-X10-XHwrFrdfry_mi0JzLlPBhRKmQyxnytpOs1YhINZ1nr6VFnhZy5ZzY6VprRAVaFCs42JW69YqUSKfkC-73m3wTwPG1GxcNLjOC6EfYlNyISVUUMmMwg41wccY0Dbb4DY6_GwYNG9em-y1efPa7L3myMm-fWg32P0LvIvMwOkO-Bv1Q-jzsv_v-wOmLoVU</recordid><startdate>20200311</startdate><enddate>20200311</enddate><creator>Xu, Shiqi</creator><creator>Fan, Fengjiao</creator><creator>Liu, Hanxiong</creator><creator>Cheng, Shuzhen</creator><creator>Tu, Maolin</creator><creator>Du, Ming</creator><general>American Chemical Society</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>7X8</scope><orcidid>https://orcid.org/0000-0001-5872-8529</orcidid></search><sort><creationdate>20200311</creationdate><title>Novel Anticoagulant Peptide from Lactoferrin Binding Thrombin at the Active Site and Exosite‑I</title><author>Xu, Shiqi ; Fan, Fengjiao ; Liu, Hanxiong ; Cheng, Shuzhen ; Tu, Maolin ; Du, Ming</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a336t-3585cdee278ffda1b8e0ee99856b6f03296b33cf6cbf5540a081d3579abf852e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Amino Acid Sequence</topic><topic>Animals</topic><topic>Anticoagulants - chemistry</topic><topic>Binding Sites</topic><topic>Catalytic Domain</topic><topic>Cattle</topic><topic>Fibrinogen - chemistry</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Lactoferrin - chemistry</topic><topic>Molecular Docking Simulation</topic><topic>Peptides - chemistry</topic><topic>Protein Binding</topic><topic>Thrombin - chemistry</topic><topic>Thrombin Time</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Xu, Shiqi</creatorcontrib><creatorcontrib>Fan, Fengjiao</creatorcontrib><creatorcontrib>Liu, Hanxiong</creatorcontrib><creatorcontrib>Cheng, Shuzhen</creatorcontrib><creatorcontrib>Tu, Maolin</creatorcontrib><creatorcontrib>Du, Ming</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Journal of agricultural and food chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Xu, Shiqi</au><au>Fan, Fengjiao</au><au>Liu, Hanxiong</au><au>Cheng, Shuzhen</au><au>Tu, Maolin</au><au>Du, Ming</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Anticoagulant Peptide from Lactoferrin Binding Thrombin at the Active Site and Exosite‑I</atitle><jtitle>Journal of agricultural and food chemistry</jtitle><addtitle>J. Agric. Food Chem</addtitle><date>2020-03-11</date><risdate>2020</risdate><volume>68</volume><issue>10</issue><spage>3132</spage><epage>3139</epage><pages>3132-3139</pages><issn>0021-8561</issn><eissn>1520-5118</eissn><abstract>Thrombin is currently one of the important targets for the treatment and prevention of thrombosis. At present, there are few reports on the application of lactoferrin peptides in anticoagulation. In this study, a peptide with the amino acid sequence of LRPVAAEIY (LF-LR) derived from lactoferrin was shown to possess antithrombotic activity. LF-LR (5 mM) significantly prolonged activated partial thromboplastin time, prothrombin time, and thrombin time for 13.4, 1.7, and 5.1 s, respectively. It prolonged the coagulation time of fibrinogen from 15.3 ± 0.4 to 20.2 ± 0.5 s by affecting the conformation of thrombin. Using circular dichroism analysis, LF-LR can increase the α-helix content of thrombin from 25.6 to 56.7% and made the β-sheet disappear. In addition, LF-LR also quenched fluorescence of thrombin at about 346 nm (λEx = 280 nm). By means of molecular docking, it was found that LF-LR could bind to both the active site and the exosite-I of thrombin, and the combined LYS60F, TRP60D, ASP189, LYS36, and ARG77A are typical amino acids in the two domains, respectively.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>32064873</pmid><doi>10.1021/acs.jafc.9b08094</doi><tpages>8</tpages><orcidid>https://orcid.org/0000-0001-5872-8529</orcidid></addata></record> |
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| subjects | Amino Acid Sequence Animals Anticoagulants - chemistry Binding Sites Catalytic Domain Cattle Fibrinogen - chemistry Humans Kinetics Lactoferrin - chemistry Molecular Docking Simulation Peptides - chemistry Protein Binding Thrombin - chemistry Thrombin Time |
| title | Novel Anticoagulant Peptide from Lactoferrin Binding Thrombin at the Active Site and Exosite‑I |
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