{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:11:47Z","timestamp":1787065907281,"version":"build-2736575974"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:sec>\n                    <jats:title>Objective\u2014<\/jats:title>\n                    <jats:p>Currently prescribed antiplatelet drugs have 1 common side effect\u2014an increased risk of hemorrhage and thrombocytopenia. On the contrary, bleeding defects associated with glycoprotein VI (GPVI) expression deficiency are usually slightly prolonged bleeding times. However, GPVI antagonists are lacking in clinic.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Approach and Results\u2014<\/jats:title>\n                    <jats:p>Using reverse-phase high-performance liquid chromatography and sequencing, we revealed the partial sequence of trowaglerix \u03b1 subunit, a potent specific GPVI-targeting snaclec (snake venom C-type lectin protein). Hexapeptide (Tro\u03b16 [trowaglerix a chain hexapeptide, CKWMNV]) and decapeptide (Tro\u03b110) derived from trowaglerix specifically inhibited collagen-induced platelet aggregation through blocking platelet GPVI receptor. Computational peptide design helped to design a series of Tro\u03b16\/Tro\u03b110 peptides. Protein docking studies on these decapeptides and GPVI suggest that Tro\u03b110 was bound at the lower surface of D1 domain and outer surface of D2 domain, which was at the different place of the collagen-binding site and the scFv (single-chain variable fragment) D2-binding site. The newly discovered site was confirmed by inhibitory effects of polyclonal antibodies on collagen-induced platelet aggregation. This indicates that D2 domain of GPVI is a novel and important binding epitope on GPVI-mediated platelet aggregation. Tro\u03b16\/Tro\u03b110 displayed prominent inhibitory effect of thrombus formation in fluorescein sodium-induced platelet thrombus formation of mesenteric venules and ferric chloride-induced carotid artery injury thrombosis model without prolonging the in vivo bleeding time.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions\u2014<\/jats:title>\n                    <jats:p>We develop a novel antithrombotic peptides derived from trowaglerix that acts through GPVI antagonism with greater safety\u2014no severe bleeding. The binding epitope of polypeptides on GPVI is novel and important. These hexa\/decapeptides have therapeutic potential for developing ideal small-mass GPVI antagonists for arterial thrombogenic diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/atvbaha.116.308604","type":"journal-article","created":{"date-parts":[[2017,6,8]],"date-time":"2017-06-08T21:10:28Z","timestamp":1496956228000},"page":"1307-1314","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":23,"title":["Trowaglerix Venom Polypeptides As a Novel Antithrombotic Agent by Targeting Immunoglobulin-Like Domains of Glycoprotein VI in Platelet"],"prefix":"10.1161","volume":"37","author":[{"given":"Chien-Hsin","family":"Chang","sequence":"first","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ching-Hu","family":"Chung","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Shu","family":"Tu","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cheng-Chieh","family":"Tsai","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chun-Chieh","family":"Hsu","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui-Chin","family":"Peng","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yufeng J.","family":"Tseng","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tur-Fu","family":"Huang","sequence":"additional","affiliation":[{"name":"From the Graduate Institute of Pharmacology, College of Medicine (C.-H.C., C.-C.H., H.-C.P., T.-F.H.), Graduate Institute of Biomedical Electronics and Bioinformatics (Y.-S.T., C.-C.T., Y.J.T.), and Department of Computational Science and Information Engineering (Y.J.T.), National Taiwan University, Taipei; and Department of Medicine, Mackay Medical College, New Taipei City, Taiwan (C.-H.C.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(06)68770-9"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm1102-1227"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1177\/0218492312445142"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.2147\/JBM.S25421"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-03-0717"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114318"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.03233.x"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1159\/000092414"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxicon.2005.02.022"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M300199200"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.272.21.13576"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2006-01-010215"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V91.2.491"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406342200"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2003-01-0308"},{"key":"e_1_3_5_17_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi801820q"},{"key":"e_1_3_5_18_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1538-7836.2008.02914.x"},{"key":"e_1_3_5_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2004.06.046"},{"key":"e_1_3_5_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.110.980623"},{"key":"e_1_3_5_21_2","first-page":"370","volume-title":"Introduction to Algorithms","author":"Leiserson CE","year":"2001","unstructured":"Leiserson CE, Rivest RL, Stein C, Cormen TH. 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