| fullrecord |
[{"key": "dc.contributor.advisor", "value": "Pentik\u00e4inen, Olli", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Postila, Pekka", "language": "", "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Jokinen, Elmeri", "language": "", "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2018-09-13T07:18:41Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2018-09-13T07:18:41Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2018", "language": "", "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/59497", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Virtuaaliseulonnassa uusia potentiaalisia l\u00e4\u00e4keaineita pyrit\u00e4\u00e4n tunnistamaan hy\u00f6dynt\u00e4m\u00e4ll\u00e4 tietoa sairauteen liittyv\u00e4n proteiinin rakenteesta ja ligandeista. T\u00e4m\u00e4n tutkimuksen tarkoituksena oli k\u00e4ytt\u00e4\u00e4 virtuaaliseulontaa uusien fosfodiesteraasi 10A (engl. phosphodiesterase 10A, PDE10A) \u2013 est\u00e4jien l\u00f6yt\u00e4miseksi. PDE10A toimii aivojen motorisia ja kognitiivisia toimintoja hallinnoivilla alueilla ja se on yhdistetty esimerkiksi skitsofrenian ja Huntingtonin taudin kehittymiseen. Ty\u00f6ss\u00e4 luotiin ligandin muodon ja elektrostaattiset ominaisuudet kuvaavia sitoutumismalleja sek\u00e4 ligandipohjaisia, kvantitatiiviseen rakenne-aktiivisuussuhteeseen perustuvia malleja. Malleilla seulottiin n. 140 000 l\u00e4\u00e4kkeenkaltaista molekyyli\u00e4 sis\u00e4lt\u00e4nyt tietokanta. Lupaavimpien molekyylien sitoutumiskonformaatioiden tarkempaan arviointiin k\u00e4ytettiin telakointia ja sitoutumisenergialaskentaa. Parhaan ennusteen saaneet molekyylit testattiin kokeellisesti ja n\u00e4ist\u00e4 kolmelle m\u00e4\u00e4ritettiin mikromolaarinen IC50-arvo. Uusien PDE10A-est\u00e4jien aktiivisuuden ennustettiin perustuvan erityisesti Q716- ja Y683-aminohappojen kanssa muodostuneisiin vetysidoksiin. Tutkimuksen tulokset tarjoavat l\u00e4ht\u00f6kohdan uusien PDE10A:han kohdistuvien l\u00e4\u00e4keainemolekyylien kehitt\u00e4miseen. Luodut sitoutumisennusteet mahdollistavat l\u00f6ydettyjen est\u00e4j\u00e4molekyylien sitoutumisominaisuuksien parantamisen hy\u00f6dynt\u00e4m\u00e4ll\u00e4 kattavammin PDE10A:n sitoutumistaskussa havaitut potentiaaliset vuorovaikutuskohdat.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "In virtual screening, information about the structure and ligands of a disease-related protein is used to identify new potential drug candidates. The aim of this study was to utilize virtual screening to discover novel phosphodiesterase 10A (PDE10A) inhibitors. PDE10A operates in regions of brain related to motoric and cognitive functions and it has been linked to several diseases, such as schizophrenia and Huntington\u2019s disease. In this study, models based on ligand shape and electrostatics and on ligand-based quantitative structure-acitivity relationship were created. The models were used to virtually screen a database of 140 000 drug-like molecules. Binding conformations of the most promising drug candidates were evaluated more precisely by using molecular docking and binding energy calculations. The best candidates were tested experimentally. Three new PDE10A inhibitors with micromolar IC50-values were discovered. Activity of the new inhibitors was predicted to be based especially on hydrogen bonding with the Q716 and Y683 residues in the PDE10A binding cavity. The results of this study provide a starting point for development of new potent drug molecules for PDE10A. The binding predictions created in this study enable improvement of the binding properties of the discovered inhibitors by a more comprehensive utilization of the potential interaction sites observed in the PDE10A binding cavity.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by Paivi Vuorio (paelvuor@jyu.fi) on 2018-09-13T07:18:41Z\nNo. of bitstreams: 0", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2018-09-13T07:18:41Z (GMT). No. of bitstreams: 0\n Previous issue date: 2018", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "49", "language": "", "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.language.iso", "value": "fin", "language": null, "element": "language", "qualifier": "iso", "schema": "dc"}, {"key": "dc.rights", "value": "In Copyright", "language": "en", "element": "rights", "qualifier": null, "schema": "dc"}, {"key": "dc.subject.other", "value": "rationaalinen l\u00e4\u00e4keainesuunnittelu", "language": "", "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Uusia fosfodiesteraasi 10A-est\u00e4ji\u00e4 virtuaalisen l\u00e4\u00e4keaineseulonnan avulla", "language": "", "element": "title", "qualifier": null, "schema": "dc"}, {"key": "dc.type", "value": "master thesis", "language": null, "element": "type", "qualifier": null, "schema": "dc"}, {"key": "dc.identifier.urn", "value": "URN:NBN:fi:jyu-201809134099", "language": "", "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Matemaattis-luonnontieteellinen tiedekunta", "language": "fi", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.faculty", "value": "Faculty of Sciences", "language": "en", "element": "contributor", "qualifier": "faculty", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Bio- ja ymp\u00e4rist\u00f6tieteiden laitos", "language": "fi", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.department", "value": "Department of Biological and Environmental Science", "language": "en", "element": "contributor", "qualifier": "department", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Solu- ja molekyylibiologia", "language": "fi", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "dc.subject.discipline", "value": "Cell and molecular biology", "language": "en", "element": "subject", "qualifier": "discipline", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": "", "element": "contractresearch", "qualifier": "funding", "schema": "yvv"}, {"key": "dc.type.coar", "value": "http://purl.org/coar/resource_type/c_bdcc", "language": null, "element": "type", "qualifier": "coar", "schema": "dc"}, {"key": "dc.rights.accesslevel", "value": "openAccess", "language": null, "element": "rights", "qualifier": "accesslevel", "schema": "dc"}, {"key": "dc.type.publication", "value": "masterThesis", "language": null, "element": "type", "qualifier": "publication", "schema": "dc"}, {"key": "dc.subject.oppiainekoodi", "value": "4013", "language": "", "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "skitsofrenia", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "l\u00e4\u00e4kesuunnittelu", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "Huntingtonin tauti", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}]
|