{ "labelLang" : "hun", "responseDate" : "2024-03-28 19:51", "content" : { "otype" : "JournalArticle", "mtid" : 30422614, "status" : "APPROVED", "published" : true, "comment" : "Physiological-chemical Institute, Department of Physical Biochemistry, University of Tübingen, Germany \n Rutgers University, Department of Chemistry and Chemical Biology, Piscataway, NJ, United States \n Physiological-chemical Institute, University of Tübingen, Hoppe-Seyler-Str. 4, D-72076 Tübingen, Germany \n Cited By :29 \n Export Date: 24 July 2023 \n CODEN: EJBCA \n Correspondence Address: Kapurniotu, A.; Physiological-Chemical Institute, Hoppe-Seyler-Str. 4, D-72076 Tübingen, Germany; email: afroditi.kapurniotu@uni-tuebingen.de", "unhandledTickets" : 0, "deleted" : false, "lastRefresh" : "2023-07-24T11:16:17.482+0000", "lastModified" : "2020-03-20T17:07:21.318+0000", "created" : "2019-02-05T11:48:15.320+0000", "creator" : { "otype" : "Admin", "mtid" : 10030548, "link" : "/api/admin/10030548", "label" : "Lövei Anett (ELTE TTK 5-ös admin)", "familyName" : "Lövei", "givenName" : "Anett", "published" : true, "oldId" : 10030548, "snippet" : true }, "lastDuplumSearch" : "2023-11-10T11:07:40.207+0000", "core" : false, "citation" : true, "publicationPending" : false, "type" : { "otype" : "PublicationType", "mtid" : 24, "link" : "/api/publicationtype/24", "label" : "Folyóiratcikk", "code" : 24, "otypeName" : "JournalArticle", "listPosition" : 1, "published" : true, "oldId" : 24, "snippet" : true }, "subType" : { "otype" : "SubType", "mtid" : 10000059, "link" : "/api/subtype/10000059", "label" : "Szakcikk (Folyóiratcikk)", "name" : "Szakcikk", "nameEng" : "Article", "docType" : { "otype" : "PublicationType", "mtid" : 24, "link" : "/api/publicationtype/24", "label" : "Folyóiratcikk", "code" : 24, "otypeName" : "JournalArticle", "listPosition" : 1, "published" : true, "oldId" : 24, "snippet" : true }, "listPosition" : 101, "published" : true, "oldId" : 10000059, "snippet" : true }, "category" : { "otype" : "Category", "mtid" : 1, "link" : "/api/category/1", "label" : "Tudományos", "published" : true, "oldId" : 1, "snippet" : true }, "languages" : [ { "otype" : "Language", "mtid" : 10002, "link" : "/api/language/10002", "label" : "Angol", "name" : "Angol", "nameEng" : "English", "published" : true, "oldId" : 2, "snippet" : true } ], "firstAuthor" : "Kazantzis, A", "authorships" : [ { "otype" : "PersonAuthorship", "mtid" : 85191824, "link" : "/api/authorship/85191824", "label" : "Kazantzis, A", "listPosition" : 1, "share" : 0.0, "first" : true, "last" : false, "familyName" : "Kazantzis", "givenName" : "A", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 85191825, "link" : "/api/authorship/85191825", "label" : "Waldner, M", "listPosition" : 2, "share" : 0.0, "first" : false, "last" : false, "familyName" : "Waldner", "givenName" : "M", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 85191826, "link" : "/api/authorship/85191826", "label" : "Taylor, JW", "listPosition" : 3, "share" : 0.0, "first" : false, "last" : false, "familyName" : "Taylor", "givenName" : "JW", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true }, { "otype" : "PersonAuthorship", "mtid" : 85191827, "link" : "/api/authorship/85191827", "label" : "Kapurniotu, A", "listPosition" : 4, "share" : 0.0, "first" : false, "last" : true, "familyName" : "Kapurniotu", "givenName" : "A", "authorTyped" : true, "editorTyped" : false, "otherTyped" : false, "type" : { "otype" : "AuthorshipType", "mtid" : 1, "link" : "/api/authorshiptype/1", "label" : "Szerző", "code" : 0, "published" : true, "oldId" : 0, "snippet" : true }, "published" : false, "snippet" : true } ], "title" : "Conformationally constrained human calcitonin (hCt) analogues reveal a critical role of sequence 17-21 for the oligomerization state and bioactivity of hCt", "identifiers" : [ { "otype" : "PublicationIdentifier", "mtid" : 15172617, "link" : "/api/publicationidentifier/15172617", "label" : "DOI: 10.1046/j.0014-2956.2001.02689.x", "source" : { "otype" : "PlainSource", "mtid" : 6, "link" : "/api/publicationsource/6", "label" : "DOI", "type" : { "otype" : "PublicationSourceType", "mtid" : 10001, "link" : "/api/publicationsourcetype/10001", "label" : "DOI", "mayHaveOa" : true, "published" : true, "snippet" : true }, "name" : "DOI", "nameEng" : "DOI", "linkPattern" : "https://doi.org/@@@", "publiclyVisible" : true, "published" : true, "oldId" : 6, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "10.1046/j.0014-2956.2001.02689.x", "realUrl" : "https://doi.org/10.1046/j.0014-2956.2001.02689.x", "published" : false, "snippet" : true }, { "otype" : "PublicationIdentifier", "mtid" : 15172616, "link" : "/api/publicationidentifier/15172616", "label" : "WoS: 000174059100005", "source" : { "otype" : "PlainSource", "mtid" : 1, "link" : "/api/publicationsource/1", "label" : "WoS", "type" : { "otype" : "PublicationSourceType", "mtid" : 10003, "link" : "/api/publicationsourcetype/10003", "label" : "Indexelő adatbázis", "mayHaveOa" : false, "published" : true, "snippet" : true }, "name" : "WoS", "nameEng" : "WoS", "linkPattern" : "https://www.webofscience.com/wos/woscc/full-record/@@@", "publiclyVisible" : true, "published" : true, "oldId" : 1, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "000174059100005", "realUrl" : "https://www.webofscience.com/wos/woscc/full-record/000174059100005", "published" : false, "snippet" : true }, { "otype" : "PublicationIdentifier", "mtid" : 24196029, "link" : "/api/publicationidentifier/24196029", "label" : "Scopus: 0036183529", "source" : { "otype" : "PlainSource", "mtid" : 3, "link" : "/api/publicationsource/3", "label" : "Scopus", "type" : { "otype" : "PublicationSourceType", "mtid" : 10003, "link" : "/api/publicationsourcetype/10003", "label" : "Indexelő adatbázis", "mayHaveOa" : false, "published" : true, "snippet" : true }, "name" : "Scopus", "linkPattern" : "http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-@@@", "publiclyVisible" : true, "published" : true, "oldId" : 3, "snippet" : true }, "validState" : "IDENTICAL", "idValue" : "0036183529", "realUrl" : "http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-0036183529", "published" : false, "snippet" : true } ], "journal" : { "otype" : "Journal", "mtid" : 1485, "link" : "/api/journal/1485", "label" : "EUROPEAN JOURNAL OF BIOCHEMISTRY 0014-2956 1432-1033 1742-464X", "pIssn" : "0014-2956", "eIssn" : "1432-1033", "reviewType" : "REVIEWED", "noIF" : false, "sciIndexed" : true, "scopusIndexed" : true, "lang" : "FOREIGN", "hungarian" : false, "published" : true, "oldId" : 1485, "snippet" : true }, "volume" : "269", "issue" : "3", "firstPage" : "780", "lastPage" : "791", "firstPageOrInternalIdForSort" : "780", "pageLength" : 12, "publishedYear" : 2002, "abstractText" : "Calcitonin (Ct) is a 32-residue peptide hormone that is mainly known for its hypocalcemic effect and the inhibition of bone resorption. Our previous studies have led to potent side-chain lactam-bridged human Ct (hCt) analogues [Kapurniotu, A. Kayed, R., Taylor, J.W. & Voelter W. (1999) Eur. J. Biochem. 265. 606-618 Kapurniotu, A. & Taylor. J.W. (1995) J. Med. Chem. 38, 836-847]. We have hypothesized that a possibly type I beta turn beta sheet conformation in the region 17-21 may play an important role in hCt bioactivity. To investigate this hypothesis, analogues of the potent hCt agonist cyclo17,21-[Asp17,Lys21]hCt (1) bearing type I (and II') or 11 beta turn-promoting substituents at positions 18 and 19 were designed, synthesized and their solution conformations, human Ct receptor binding affinities and in vivo hypocalcemic potencies were assessed. The novel analogues include cyclo17,21-[Asp17,D-Phe19. Lys21]hCt (2). cyclo17,21-[Asp17.Aib18,Lys21]hCt (3). cyclo 17.21-[Asp17,D-Lys18,Lys21]hCt (4), corresponding partial sequence peptides containing the lactam-bridged region 16 22, and nonbridged control peptides. Only 1 showed a higher Ct receptor binding affinity than hCt, whereas analogues 2-4 had similar receptor alfinities to hCt. In the in vivo hypocalcemic assay, 3 and 4 were as potent as 1, whereas 2 completely lost the high potency of 1, suggesting that type I (and II') beta turn-promoting substituents are fully compatible with in vivo bioactivity. CD spectroscopy showed that analogues 1-4 were markedly beta sheet-stabilized compared to hCt and indicated the presence of distinct beta turn conformeric populations in each of the analogues. Unexpectedly, the D-amino acid- or Aib-containing cyclic analogues 2-4 but not 1 or hCt self-associated into SDS denaturation-stable dimers. Our results demonstrate a crucial role of the conformational and topological features of the residues in sequence 17-21 and in particular of residues 18 and 19 for human Ct receptor binding and in vivo bioactivity and also for the self association state of hCt. These results may assist to delineate the structure-function relationships or hCt and to design novel hCt agonists for the treatment of osteoporosis and other bone-disorder-related diseases.", "subjects" : [ { "otype" : "Classification", "mtid" : 10545, "link" : "/api/classification/10545", "label" : "Biológiai tudományok", "published" : true, "snippet" : true } ], "keywords" : [ { "otype" : "Keyword", "mtid" : 7740, "link" : "/api/keyword/7740", "label" : "Dimerization", "published" : true, "oldId" : 7740, "snippet" : true }, { "otype" : "Keyword", "mtid" : 18733, "link" : "/api/keyword/18733", "label" : "receptor binding", "published" : true, "oldId" : 18733, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1557731, "link" : "/api/keyword/1557731", "label" : "human calcitonin", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1557732, "link" : "/api/keyword/1557732", "label" : "beta turn/beta sheet conformation", "published" : true, "snippet" : true }, { "otype" : "Keyword", "mtid" : 1557733, "link" : "/api/keyword/1557733", "label" : "hypocalcemic activity", "published" : true, "snippet" : true } ], "digital" : null, "printed" : null, "sourceYear" : 2019, "foreignEdition" : true, "foreignLanguage" : true, "fullPublication" : true, "conferencePublication" : false, "nationalOrigin" : false, "missingAuthor" : false, "oaType" : "NONE", "oaCheckDate" : "2023-07-24", "oaFree" : false, "citationCount" : 0, "citationCountUnpublished" : 0, "citationCountWoOther" : 0, "independentCitCountWoOther" : 0, "doiCitationCount" : 0, "wosCitationCount" : 0, "scopusCitationCount" : 0, "independentCitationCount" : 0, "unhandledCitationCount" : 0, "citingPubCount" : 0, "independentCitingPubCount" : 0, "unhandledCitingPubCount" : 0, "citedPubCount" : 3, "citedCount" : 3, "ratings" : [ { "otype" : "SjrRating", "mtid" : 6060887, "link" : "/api/sjrrating/6060887", "label" : "sjr:Q1 (2002) Scopus - Biochemistry EUROPEAN JOURNAL OF BIOCHEMISTRY 0014-2956 1432-1033 1742-464X", "listPos" : 48, "rankValue" : 0.24, "type" : "journal", "ratingType" : { "otype" : "RatingType", "mtid" : 10002, "link" : "/api/ratingtype/10002", "label" : "sjr", "code" : "sjr", "published" : true, "snippet" : true }, "subject" : { "otype" : "ClassificationExternal", "mtid" : 1303, "link" : "/api/classificationexternal/1303", "label" : "Scopus - Biochemistry", "published" : true, "oldId" : 1303, "snippet" : true }, "ranking" : "Q1", "calculation" : "DIRECT", "published" : true, "oldId" : 6060887, "snippet" : true } ], "ratingsForSort" : "Q1", "hasCitationDuplums" : false, "userChangeableUntil" : "2020-06-18T16:07:21.172+0000", "directInstitutesForSort" : "", "ownerAuthorCount" : 2, "ownerInstituteCount" : 13, "directInstituteCount" : 0, "authorCount" : 4, "contributorCount" : 0, "hasQualityFactor" : true, "link" : "/api/publication/30422614", "label" : "Kazantzis A et al. Conformationally constrained human calcitonin (hCt) analogues reveal a critical role of sequence 17-21 for the oligomerization state and bioactivity of hCt. (2002) EUROPEAN JOURNAL OF BIOCHEMISTRY 0014-2956 1432-1033 1742-464X 269 3 780-791", "template" : "