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New ligands are necessary tools for biomedical research and the detection of L1CAM. Here, DNA aptamer yly12 against L1CAM was optimized to have much stronger binding affinity (10\u201324 fold) at room temperature and 37 \u00b0C via sequence mutation and extension. This interaction study revealed that the optimized aptamers (yly20 and yly21) adopted a hairpin structure containing two loops and two stems. The key nucleotides for aptamer binding mainly located in loop I and its adjacent area. Stem I mainly played the role of stabilizing the binding structure. The yly-series aptamers were demonstrated to bind the Ig6 domain of L1CAM. This study reveals a detailed molecular mechanism for the interaction between yly-series aptamers and L1CAM and provides guidance for drug development and detection probe design against L1CAM.<\/jats:p>","DOI":"10.3390\/ijms24108612","type":"journal-article","created":{"date-parts":[[2023,5,12]],"date-time":"2023-05-12T02:36:59Z","timestamp":1683859019000},"page":"8612","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Structural Optimization and Interaction Study of a DNA Aptamer to L1 Cell Adhesion Molecule"],"prefix":"10.3390","volume":"24","author":[{"given":"Zhenhao","family":"Long","sequence":"first","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5121-053X","authenticated-orcid":false,"given":"Tao","family":"Bing","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangru","family":"Zhang","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Sheng","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuang","family":"Zu","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Li","sequence":"additional","affiliation":[{"name":"Zhejiang Cancer Hospital, The Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China"},{"name":"School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangjun","family":"Liu","sequence":"additional","affiliation":[{"name":"Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical 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Living Biosystems, CAS Research and Education Center for Excellence in Molecular Sciences, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Chemical Sciences, University of Chinese Academy of Sciences, Beijing 100049, China"},{"name":"School of Molecular Medicine, Hangzhou Institute for Advanced Study, University of Chinese Academy of Sciences, Hangzhou 310013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Van der Maten, M., Reijnen, C., Pijnenborg, J.M.A., and Zegers, M.M. 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