{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T03:27:43Z","timestamp":1762918063540,"version":"build-2065373602"},"reference-count":50,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2019,12,21]],"date-time":"2019-12-21T00:00:00Z","timestamp":1576886400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004663","name":"Ministry of Science and Technology, Taiwan","doi-asserted-by":"publisher","award":["107-2320-B-715-004-MY3"],"award-info":[{"award-number":["107-2320-B-715-004-MY3"]}],"id":[{"id":"10.13039\/501100004663","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014804","name":"Mackay Medical College","doi-asserted-by":"publisher","award":["MMC-1071B25","MMC-1072B33","MMC-1081B14"],"award-info":[{"award-number":["MMC-1071B25","MMC-1072B33","MMC-1081B14"]}],"id":[{"id":"10.13039\/501100014804","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Life-threatening thrombocytopenia and bleeding, common side effects of clinically available \u03b1IIb\u03b23 antagonists, are associated with the induction of ligand-induced integrin conformational changes and exposure of ligand-induced binding sites (LIBSs). To address this issue, we examined intrinsic mechanisms and structure\u2013activity relationships of purified disintegrins, from Protobothrops flavoviridis venom (i.e., Trimeresurus flavoviridis), TFV-1 and TFV-3 with distinctly different pro-hemorrhagic tendencies. TFV-1 with a different \u03b1IIb\u03b23 binding epitope from that of TFV-3 and chimeric 7E3 Fab, i.e., Abciximab, decelerates \u03b1IIb\u03b23 ligation without causing a conformational change in \u03b1IIb\u03b23, as determined with the LIBS antibody, AP5, and the mimetic, drug-dependent antibody (DDAb), AP2, an inhibitory monoclonal antibody raised against \u03b1IIb\u03b23. Consistent with their different binding epitopes, a combination of TFV-1 and AP2 did not induce Fc\u03b3RIIa-mediated activation of the ITAM\u2013Syk\u2013PLC\u03b32 pathway and platelet aggregation, in contrast to the clinical antithrombotics, abciximab, eptifibatide, and disintegrin TFV-3. Furthermore, TFV-1 selectively inhibits G\u03b113-mediated platelet aggregation without affecting talin-driven clot firmness, which is responsible for physiological hemostatic processes. At equally efficacious antithrombotic dosages, TFV-1 caused neither severe thrombocytopenia nor bleeding in Fc\u03b3RIIa-transgenic mice. Likewise, it did not induce hypocoagulation in human whole blood in the rotational thromboelastometry (ROTEM) assay used in perioperative situations. In contrast, TFV-3 and eptifibatide exhibited all of these hemostatic effects. Thus, the \u03b1IIb\u03b23 antagonist, TFV-1, efficaciously prevents arterial thrombosis without adversely affecting hemostasis.<\/jats:p>","DOI":"10.3390\/toxins12010011","type":"journal-article","created":{"date-parts":[[2019,12,23]],"date-time":"2019-12-23T03:23:12Z","timestamp":1577071392000},"page":"11","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["A Novel \u03b1IIb\u03b23 Antagonist from Snake Venom Prevents Thrombosis without Causing Bleeding"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5855-9785","authenticated-orcid":false,"given":"Yu-Ju","family":"Kuo","sequence":"first","affiliation":[{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3096-8974","authenticated-orcid":false,"given":"Ching-Hu","family":"Chung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tzu-Yu","family":"Pan","sequence":"additional","affiliation":[{"name":"Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Woei-Jer","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, National Cheng Kung University Medical College, Tainan 70101, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tur-Fu","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Medicine, Mackay Medical College, New Taipei City 25245, Taiwan"},{"name":"Graduate Institute of Pharmacology, College of Medicine, National Taiwan University, Taipei 10051, Taiwan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1161\/CIRCRESAHA.112.300570","article-title":"Integrin alphaiibbeta3: From discovery to efficacious therapeutic target","volume":"112","author":"Bledzka","year":"2013","journal-title":"Circ. 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