{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T18:28:16Z","timestamp":1768588096907,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T00:00:00Z","timestamp":1768348800000},"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":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Expanding the chemical diversity of DNA\u2013encoded libraries (DELs) is crucial for identifying binders to emerging drug targets using DEL technology. In the present study, as part of our ongoing efforts to develop on\u2013DNA diazide platforms (D\u2013DAPs)\u2014platform molecules possessing both aromatic and aliphatic azide groups on a single core reactive scaffold\u2014we designed and synthesized a new compact diazide platform, designated as a compact D\u2013DAP (C\u2013D\u2013DAP). This molecule is based on a low\u2013molecular\u2013weight reactive scaffold, 3\u2013azido\u20135\u2013(azidomethyl)benzoic acid, to facilitate small\u2013molecule drug discovery targeting enzymes and G protein\u2013coupled receptors (GPCRs). Furthermore, we established two distinct stepwise warhead construction strategies that exploit the chemoselective transformations of the azide groups in the C\u2013D\u2013DAP, which exhibit different reactivities. In addition, four virtual DELs were generated based on stepwise warhead elaboration from the C\u2013D\u2013DAP scaffold. Comparative chemical diversity analysis against bioactive compounds from ChEMBL revealed that these virtual libraries populate structural regions that are sparsely represented among known molecules. Each virtual library also occupies a distinct region of structural space relative to the others and displays intermediate quantitative estimate of drug\u2013likeness (QED) values.<\/jats:p>","DOI":"10.3390\/ijms27020828","type":"journal-article","created":{"date-parts":[[2026,1,14]],"date-time":"2026-01-14T11:01:14Z","timestamp":1768388474000},"page":"828","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["On\u2013DNA Platform Molecules Based on a Diazide Scaffold II: A Compact Diazide Platform Designed for Small\u2013Molecule Drug Discovery"],"prefix":"10.3390","volume":"27","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":"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":[[2026,1,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1265","DOI":"10.1021\/acsptsci.1c00118","article-title":"DNA-encoded chemical libraries: A comprehensive review with succesful stories and future challenges","volume":"4","author":"Donckele","year":"2021","journal-title":"ACS Pharmacol. 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