{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,4]],"date-time":"2025-12-04T19:21:45Z","timestamp":1764876105087,"version":"3.46.0"},"reference-count":41,"publisher":"Wiley","issue":"23","license":[{"start":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T00:00:00Z","timestamp":1760572800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"The Japan Agency for Medical Research and Development","doi-asserted-by":"publisher","award":["JP22ak0101130","JP24ek0109720"],"award-info":[{"award-number":["JP22ak0101130","JP24ek0109720"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"KAKENHI","doi-asserted-by":"publisher","award":["22H05049","25H01283"],"award-info":[{"award-number":["22H05049","25H01283"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2025,11,28]]},"abstract":"<jats:p>Aptamer is a promising therapeutic modality, offering strong target affinity and target versatility. In the previous studies, DNA aptamers with potent thrombin inhibitory activity, M08s\u20101 and its bivalent derivatives, have been developed as novel anticoagulant agents. Among them, the heterobivalent aptamer Pse08\u201029 exhibits the most potent ex\u2009vivo anticoagulant activity, surpassing the approved drug argatroban. However, its long oligonucleotide chains composed of 106 nucleotides may hinder its drug development due to limited chemical synthetic efficiency. Here, a segmented form of Pse08\u201029 composed of two DNA strands, assembled via a sticky end\u2010type strategy, is developed. The cleavage positions and optimal linker lengths are studied based on the anticoagulant activity and structural stability, revealing that a few cleavage sites within the duplex linker region are acceptable without losing the activity. Surprisingly, one of such aptamers, Stick08\u201029(19\u2010B), shows the significantly enhanced serum stability compared to Pse08\u201029, despite the two nick\u2010like sites existing. Finally, selected bivalent aptamers, consisting of two split DNA strands (&lt;65\u2009mer), exhibit the high anticoagulant activity as well as Pse08\u201029. This highlights not only efficient nucleobase reduction with preserved function but also a new design strategy for bivalent aptamers.<\/jats:p>","DOI":"10.1002\/cmdc.202500688","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T22:35:02Z","timestamp":1760654102000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design and Evaluation of Sticky End\u2010Type Bivalent DNA Aptamers Containing M08s\u20101 as Anticoagulant Agents"],"prefix":"10.1002","volume":"20","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3973-973X","authenticated-orcid":false,"given":"Maasa","family":"Yokomori","sequence":"first","affiliation":[{"name":"Graduate School of Arts and Sciences Department of Life Sciences The University of Tokyo  3\u20108\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20138902 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mizuki","family":"Murasawa","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences Department of Life Sciences The University of Tokyo  3\u20108\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20138902 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muneyuki","family":"Matsuo","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences Department of Life Sciences The University of Tokyo  3\u20108\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20138902 Japan"},{"name":"Graduate School of Integrated Sciences for Life Hiroshima University  1\u20103\u20101 Kagamiyama, Higashi\u2010hiroshima Hiroshima 739\u20138526 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masanobu","family":"Nagano","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences Department of Life Sciences The University of Tokyo  3\u20108\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20138902 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6052-1399","authenticated-orcid":false,"given":"Keitaro","family":"Yoshimoto","sequence":"additional","affiliation":[{"name":"Graduate School of Arts and Sciences Department of Life Sciences The University of Tokyo  3\u20108\u20101 Komaba, Meguro\u2010ku Tokyo 153\u20138902 Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"doi-asserted-by":"publisher","key":"e_1_2_8_2_1","DOI":"10.1038\/s41392-024-02035-4"},{"doi-asserted-by":"publisher","key":"e_1_2_8_3_1","DOI":"10.1089\/nat.2023.0068"},{"key":"e_1_2_8_4_1","first-page":"774","volume":"22","author":"Mullard A.","year":"2023","journal-title":"Nat. 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