{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T20:49:59Z","timestamp":1773089399124,"version":"3.50.1"},"reference-count":20,"publisher":"Wiley","issue":"13","license":[{"start":{"date-parts":[[2020,9,28]],"date-time":"2020-09-28T00:00:00Z","timestamp":1601251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["1UG3DA048351"],"award-info":[{"award-number":["1UG3DA048351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Labelled Comp Radiopharmac"],"published-print":{"date-parts":[[2020,11]]},"abstract":"<jats:p>A deuterated hapten was designed and synthesized that will be essential for a future study of residual hapten and stability of a hapten\u2010protein conjugate. This hapten, 6\u2010AmHap, was chosen for a heroin vaccine that is now slated for a Phase 1 clinical trial. A maleimide\u2010thiol bioconjugation strategy was successfully applied to our heroin vaccine to connect the hapten 6\u2010AmHap with an immunogenic carrier protein (tetanus toxoid, TT) through a trityl\u2010protected 3\u2010mercaptopropanamide linker. The antibodies induced by the vaccine have been found to have activity against several opioids, including heroin and its metabolites, and, importantly, leave alternate pain treatment medications such as methadone untouched. To the best of our knowledge, no other hapten for a heroin vaccine has been deuterated, yet this tool may prove to be of great importance in the study of residual hapten during product release and the long\u2010term stability program of a hapten\u2010protein conjugate as part of FDA regulatory requirements. Hydrocodone was the starting material for the synthesis of the deuterated 6\u2010AmHap, with a stable amide at C6 and a 3\u2010mercaptopropanamide linker attached at C3. The desired deuterated product was prepared as the disulfide, 3,3\u2032\u2010disulfanediylbis(<jats:italic>N<\/jats:italic>\u2010((7<jats:italic>S<\/jats:italic>,7a<jats:italic>R<\/jats:italic>,12b<jats:italic>S<\/jats:italic>)\u20107\u2010acetamido\u20103\u2010[<jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>]methyl)\u20102,3,4,4a,5,6,7,7a\u2010octahydro\u20101<jats:italic>H<\/jats:italic>\u20104,12\u2010methanobenzofuro[3,2\u2010<jats:italic>e<\/jats:italic>]isoquinolin\u20109\u2010yl)propanamide), that could be easily reduced to form the needed hapten, <jats:italic>N<\/jats:italic>\u2010((4a<jats:italic>R<\/jats:italic>,7<jats:italic>S<\/jats:italic>,7a<jats:italic>R<\/jats:italic>,12b<jats:italic>S<\/jats:italic>)\u20107\u2010acetamido\u20103\u2010[<jats:sup>2<\/jats:sup>H<jats:sub>3<\/jats:sub>]methyl]\u20102,3,4,4a,5,6,7,7a\u2010octahydro\u20101<jats:italic>H<\/jats:italic>\u20104,12\u2010methanobenzofuro[3,2\u2010<jats:italic>e<\/jats:italic>]isoquinolin\u20109\u2010yl)\u20103\u2010mercaptopropanamide.<\/jats:p>","DOI":"10.1002\/jlcr.3880","type":"journal-article","created":{"date-parts":[[2021,1,29]],"date-time":"2021-01-29T10:05:40Z","timestamp":1611914740000},"page":"564-571","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Synthesis of a deuterated 6\u2010AmHap internal standard for the determination of hapten density in a heroin vaccine drug product"],"prefix":"10.1002","volume":"63","author":[{"given":"Mariia","family":"Makarova","sequence":"first","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Department of Health and Human Services  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodell C.","family":"Barrientos","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program Walter Reed Army Institute of Research  Silver Spring Maryland USA"},{"name":"U.S. Military HIV Research Program Henry M. Jackson Foundation for the Advancement of Military Medicine  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar B.","family":"Torres","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program Walter Reed Army Institute of Research  Silver Spring Maryland USA"},{"name":"U.S. Military HIV Research Program Henry M. Jackson Foundation for the Advancement of Military Medicine  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gary R.","family":"Matyas","sequence":"additional","affiliation":[{"name":"Laboratory of Adjuvant and Antigen Research, U.S. Military HIV Research Program Walter Reed Army Institute of Research  Silver Spring Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur E.","family":"Jacobson","sequence":"additional","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Department of Health and Human Services  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8849-9736","authenticated-orcid":false,"given":"Agnieszka","family":"Sulima","sequence":"additional","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Department of Health and Human Services  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenner C.","family":"Rice","sequence":"additional","affiliation":[{"name":"Drug Design and Synthesis Section, Molecular Targets and Medications Discovery Branch, Intramural Research Program, National Institute on Drug Abuse and the National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health Department of Health and Human Services  Bethesda Maryland USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,9,28]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.15585\/mmwr.mm6911a4"},{"key":"e_1_2_10_3_1","unstructured":"NIDA.The science of drug use and addiction: the basics.2020. p.1\u201030. 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