{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T19:52:30Z","timestamp":1792785150943,"version":"4.5.0"},"reference-count":44,"publisher":"Georg Thieme Verlag KG","issue":"02","funder":[{"name":"Shanghai Municipal Health Commission Health Industry Clinical Research Project","award":["20224Y0120"],"award-info":[{"award-number":["20224Y0120"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"crossref","award":["82273293"],"award-info":[{"award-number":["82273293"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Thromb Haemost"],"published-print":{"date-parts":[[2024,2]]},"abstract":"<jats:p>Background\u2003Classical anticoagulants and antiplatelets are associated with high frequencies of bleeding complications or treatment failure when used as single agents. Thrombin plays an important role in the blood coagulation system. GP IIb\/IIIa is the central receptor of platelets, which can recognize the Arg-Gly-Asp (RGD) sequence and activate platelets.<\/jats:p>\n                  <jats:p>Material and Methods\u2003Molecular simulation and homology modeling were performed to design a novel dual-target anticoagulant short peptide (PTIP ). The activities of PTIP on coagulation and platelet in vitro were analyzed. The antithrombotic activity of PTIP was determined by pulmonary thromboembolism model, ferric chloride injury model and arteriovenous bypass thrombosis model. Bleeding effect and toxicity of PTIP were evaluated.<\/jats:p>\n                  <jats:p>Results\u2003We have constructed a novel dual-target peptide (PTIP) based on the direct thrombin inhibitor peptide (DTIP). PTIP was expressed at high levels in Pichia pastoris. PTIP interfered with thrombin-mediated coagulation and ADP-induced platelet aggregation in vitro. When injected intravenously or subcutaneously, PTIP showed potent and dose-dependent extension of aPTT and PT which were similar to DTIP; but only PTIP was capable of inhibiting platelet aggregation. PTIP (1.0 mg\/kg) decelerated thrombosis formation in venous and arterial vessels induced by FeCl3 injury. PTIP (1.0 mg\/kg) also prevented deep venous thrombosis and increased the survival rate associated with pulmonary thromboembolism. And PTIP effectively reduced thrombus length in arteriovenous bypass thrombosis model. Moreover, the antithrombotic dose of PTIP could not induce bleeding.<\/jats:p>\n                  <jats:p>Conclusion\u2003These data establish that PTIP represents a novel antithrombotic agent whose effects involve both inhibition of platelet activation and reduction of fibrin generation. And PTIP not only can be used in venous thrombosis and arterial thrombosis, it can also replace the combined treatment of antiplatelet and anticoagulant drugs in thrombotic diseases.<\/jats:p>","DOI":"10.1055\/a-2165-1000","type":"journal-article","created":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T19:06:20Z","timestamp":1693595180000},"page":"108-121","source":"Crossref","is-referenced-by-count":5,"title":["Anti-thrombotic Effects Mediated by a Novel Dual-Target Peptide Inhibiting Both Platelet Aggregation and Thrombin Activity without Causing Bleeding"],"prefix":"10.1055","volume":"124","author":[{"given":"Jinchao","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 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University, Shanghai, China"},{"name":"The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Min","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bing","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Metabolism and Molecular Medicine, Ministry of Education, School of Basic Medical Sciences, Fudan University, Shanghai, China"},{"name":"The Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 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