{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:23:56Z","timestamp":1787502236982,"version":"build-2736575974"},"reference-count":0,"publisher":"National Academy of Sciences","issue":"13","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1995,6,20]]},"abstract":"<jats:p>Very large combinatorial libraries of small molecules on solid supports can now be synthesized and each library element can be identified after synthesis by using chemical tags. These tag-encoded libraries are potentially useful in drug discovery, and, to test this utility directly, we have targeted carbonic anhydrase (carbonate dehydratase; carbonate hydro-lyase, EC 4.2.1.1) as a model. Two libraries consisting of a total of 7870 members were synthesized, and structure-activity relationships based on the structures predicted by the tags were derived. Subsequently, an active representative of each library was resynthesized (2-[N-(4-sulfamoylbenzoyl)-4'-aminocyclohexanespiro]-4-oxo-7 -hydroxy- 2,3-dihydrobenzopyran and [N-(4-sulfamoylbenzoyl)-L-leucyl]piperidine-3-carboxylic acid) and these compounds were shown to have nanomolar dissociation constants (15 and 4 nM, respectively). In addition, a focused sublibrary of 217 sulfamoylbenzamides was synthesized and revealed a clear, testable structure-activity relationship describing isozyme-selective carbonic anhydrase inhibitors.<\/jats:p>","DOI":"10.1073\/pnas.92.13.6027","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T09:13:54Z","timestamp":1149066834000},"page":"6027-6031","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["A paradigm for drug discovery employing encoded combinatorial libraries."],"prefix":"10.1073","volume":"92","author":[{"given":"J J","family":"Burbaum","sequence":"first","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M H","family":"Ohlmeyer","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J C","family":"Reader","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I","family":"Henderson","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L W","family":"Dillard","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T L","family":"Randle","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N H","family":"Sigal","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D","family":"Chelsky","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J J","family":"Baldwin","sequence":"additional","affiliation":[{"name":"Department of Biology, Pharmacopeia, Inc., Princeton, NJ 08540, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1995,6,20]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.92.13.6027","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T14:03:29Z","timestamp":1649858609000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.92.13.6027"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,6,20]]},"references-count":0,"journal-issue":{"issue":"13","published-print":{"date-parts":[[1995,6,20]]}},"alternative-id":["10.1073\/pnas.92.13.6027"],"URL":"https:\/\/doi.org\/10.1073\/pnas.92.13.6027","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,6,20]]},"assertion":[{"value":"1995-06-20","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}