{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T01:39:23Z","timestamp":1768441163617,"version":"3.49.0"},"reference-count":38,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009619","name":"The Japan Agency for Medical Research and Development","doi-asserted-by":"crossref","award":["JP22zf0227001h0001"],"award-info":[{"award-number":["JP22zf0227001h0001"]}],"id":[{"id":"10.13039\/100009619","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["IJMS"],"abstract":"<jats:p>Expanding the chemical space of DNA-encoded libraries (DELs) is desirable for identifying novel bioactive compounds and enhancing hit quality in affinity-based screening. In this study, we designed and synthesized a new on-DNA diazide platform (DAP) molecule that incorporates both aromatic and aliphatic azido groups within a single scaffold. These orthogonal azides exhibit distinct reactivity profiles, enabling a stepwise warhead construction strategy through chemoselective transformations. This approach facilitates greater structural diversity and efficient incorporation of diverse building blocks. A virtual DEL was generated based on this DAP scaffold, and its chemical space was compared with that of bioactive compounds in the ChEMBL database. The analysis revealed that this virtual library occupied a distinct and previously unexplored region of chemical space, highlighting the potential of this DAP-based strategy for discovering structurally novel DEL members with biological relevance.<\/jats:p>","DOI":"10.3390\/ijms26199501","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T15:38:55Z","timestamp":1759246735000},"page":"9501","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Development of an On-DNA Platform Molecule Bearing a Diazidestructure and Its Application to DEL Synthesis"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3764-688X","authenticated-orcid":false,"given":"Hiroyuki","family":"Miyachi","sequence":"first","affiliation":[{"name":"Lead Exploration Unit, Drug Discovery Initiative, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Koshimizu","sequence":"additional","affiliation":[{"name":"Lead Exploration Unit, Drug Discovery Initiative, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manussada","family":"Ratanasak","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3219-6007","authenticated-orcid":false,"given":"Yasuteru","family":"Shigeta","sequence":"additional","affiliation":[{"name":"Center for Computational Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8577, Ibaraki, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Suzuki","sequence":"additional","affiliation":[{"name":"Lead Exploration Unit, Drug Discovery Initiative, University of Tokyo, 7-3-1 Hongo, Bunkyo, Tokyo 113-0033, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"5381","DOI":"10.1073\/pnas.89.12.5381","article-title":"Encoded combinatorial chemistry","volume":"89","author":"Brenner","year":"1992","journal-title":"Proc. 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