{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T19:20:17Z","timestamp":1783970417630,"version":"3.55.0"},"reference-count":15,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T00:00:00Z","timestamp":1647648000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T00:00:00Z","timestamp":1647648000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001801","name":"University of Western Australia","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100001801","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["J Thromb Thrombolysis"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The poly-arginine peptides R18D and R18 represent novel potential neuroprotective treatments for acute ischaemic stroke. Here we examined whether R18D and R18 had any significant effects on the thrombolytic activity of alteplase (tPA) and tenecteplase (TNK) on clots formed from whole blood in an in vitro thrombolysis plate assay. R18D and R18 were examined at concentrations of 0.25, 0.5, 1, 2, 4, 8 and 16\u00a0\u00b5M during the 1-h thrombolytic assay. We also included the well-characterised neuroprotective NA-1 peptide as a control. R18D, R18 and NA-1 all reduced tPA or TNK percentage clot lysis by 0\u20139.35%, 0\u20133.44% and 0\u20134.8%, respectively. R18D, R18 and NA-1 had a modest and variable effect on the lag time, increasing the time to the commencement of thrombolysis by 0\u20139.9\u00a0min, 0\u20135.53\u00a0min and 0\u20137.16\u00a0min, respectively. Lastly, R18 and NA-1 appeared to increase the maximal activity of the thrombolysis reaction. In addition, the in vitro anti-excitotoxic neuroprotective efficacy of R18D and R18 was not affected by pre-incubation for 1\u20132\u00a0h or overnight with tPA or TNK, whereas only R18D retained high anti-excitotoxic neuroprotective efficacy when pre-incubated in a synthetic trypsin (TrypLE Express). The present in vitro findings suggest that neither R18D or R18 when co-administered with the thrombolytic inducing agents tPA or TNK are likely to have a significant impact when used clinically during clot thrombolysis and confirm the superior proteolytic stability of the R18D peptide.<\/jats:p>","DOI":"10.1007\/s11239-022-02642-4","type":"journal-article","created":{"date-parts":[[2022,3,19]],"date-time":"2022-03-19T06:02:51Z","timestamp":1647669771000},"page":"172-182","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of poly-arginine peptides R18D and R18 on alteplase and tenecteplase thrombolysis in vitro, and neuroprotective stability to proteolysis"],"prefix":"10.1007","volume":"54","author":[{"given":"Bruno P.","family":"Meloni","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Blacker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam B.","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neville W.","family":"Knuckey","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,3,19]]},"reference":[{"issue":"9","key":"2642_CR1","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1080\/14737175.2020.1788390","volume":"20","author":"BP Meloni","year":"2020","unstructured":"Meloni BP, Blacker DJ, Mastaglia FL, Knuckey NW (2020) Emerging cytoprotective peptide therapies for stroke. 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Expert Opin Drug Metab Toxicol 8(2):271\u2013281","journal-title":"Expert Opin Drug Metab Toxicol"}],"container-title":["Journal of Thrombosis and Thrombolysis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11239-022-02642-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s11239-022-02642-4\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s11239-022-02642-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,6]],"date-time":"2022-07-06T06:07:41Z","timestamp":1657087661000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s11239-022-02642-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,3,19]]},"references-count":15,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,7]]}},"alternative-id":["2642"],"URL":"https:\/\/doi.org\/10.1007\/s11239-022-02642-4","relation":{},"ISSN":["0929-5305","1573-742X"],"issn-type":[{"value":"0929-5305","type":"print"},{"value":"1573-742X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,3,19]]},"assertion":[{"value":"8 March 2022","order":1,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 March 2022","order":2,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"BPM and NWK are the holders of several patents regarding the use of arginine-rich peptides as neuroprotective treatments. BPM, DJB, ABE and NWK are shareholders in Argenica Therapeutics, which is a company developing R18 and R18D as stroke therapeutics. In addition, DJB is a Clinical Advisor and BPM is the Chief Scientific Officer for Argenica Therapeutics.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}},{"value":"All animal work was performed in compliance with the Animal Ethics Committee of the University of Western Australia and following the guidelines outlined by the Australian Code for the Care and Use of Animals for Scientific Purposes and adhered to the Animal Welfare Act 2002 (Western Australia). Experimentation with human samples had the approval of the Perron Institute and consent of the one author (BM).","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}]}}