{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T01:22:07Z","timestamp":1777512127971,"version":"3.51.4"},"reference-count":0,"publisher":"Proceedings of the National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1977,12]]},"abstract":"<jats:p>\n            A guanine derivative with an acyclic side chain, 2-hydroxyethoxymethyl, at position 9 has potent antiviral activity [dose for 50% inhibition (ED\n            <jats:sub>50<\/jats:sub>\n            ) = 0.1 \u03bcM] against herpes simplex virus type 1. This acyclic nucleoside analog, termed acycloguanosine, is converted to a monophosphate by a virus-specified pyrimidine deoxynucleoside (thymidine) kinase and is subsequently converted to acycloguanosine di- and triphosphates. In the uninfected host cell (Vero) these phosphorylations of acycloguanosine occur to a very limited extent. Acycloguanosine triphosphate inhibits herpes simplex virus DNA polymerase (DNA nucleotidyltransferase) 10-30 times more effectively than cellular (HeLa S3) DNA polymerase. These factors contribute to the drug's selectivity; inhibition of growth of the host cell requires a 3000-fold greater concentration of drug than does the inhibition of viral multiplication. There is, moreover, the strong possibility of chain termination of the viral DNA by incorporation of acycloguanosine.\n          <\/jats:p>\n          <jats:p>The identity of the kinase that phosphorylates acycloguanosine was determined after separation of the cellular and virus-specified thymidine kinase activities by affinity chromatography, by reversal studies with thymidine, and by the lack of monophosphate formation in a temperature-sensitive, thymidine kinase-deficient mutant of the KOS strain of herpes simplex virus type 1 (tsA1).<\/jats:p>","DOI":"10.1073\/pnas.74.12.5716","type":"journal-article","created":{"date-parts":[[2006,5,31]],"date-time":"2006-05-31T07:25:26Z","timestamp":1149060326000},"page":"5716-5720","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":1184,"title":["Selectivity of action of an antiherpetic agent, 9-(2-hydroxyethoxymethyl)guanine"],"prefix":"10.1073","volume":"74","author":[{"given":"Gertrude B.","family":"Elion","sequence":"first","affiliation":[{"name":"Department of Experimental Therapy, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Phillip A.","family":"Furman","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapy, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Fyfe","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapy, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paulo de","family":"Miranda","sequence":"additional","affiliation":[{"name":"Department of Experimental Therapy, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilia","family":"Beauchamp","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Howard J.","family":"Schaeffer","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Wellcome Research Laboratories, Burroughs Wellcome Company, Research Triangle Park, North Carolina 27709"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"341","published-online":{"date-parts":[[1977,12]]},"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.74.12.5716","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,13]],"date-time":"2022-04-13T15:17:12Z","timestamp":1649863032000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.74.12.5716"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1977,12]]},"references-count":0,"journal-issue":{"issue":"12","published-print":{"date-parts":[[1977,12]]}},"alternative-id":["10.1073\/pnas.74.12.5716"],"URL":"https:\/\/doi.org\/10.1073\/pnas.74.12.5716","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[1977,12]]},"assertion":[{"value":"1977-12-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}