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[{"key": "dc.contributor.advisor", "value": "Pentik\u00e4inen, Olli", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.advisor", "value": "Niinivehmas, Sanna", "language": null, "element": "contributor", "qualifier": "advisor", "schema": "dc"}, {"key": "dc.contributor.author", "value": "Pasanen, Mira", "language": null, "element": "contributor", "qualifier": "author", "schema": "dc"}, {"key": "dc.date.accessioned", "value": "2015-04-08T07:47:45Z", "language": null, "element": "date", "qualifier": "accessioned", "schema": "dc"}, {"key": "dc.date.available", "value": "2015-04-08T07:47:45Z", "language": null, "element": "date", "qualifier": "available", "schema": "dc"}, {"key": "dc.date.issued", "value": "2015", "language": null, "element": "date", "qualifier": "issued", "schema": "dc"}, {"key": "dc.identifier.other", "value": "oai:jykdok.linneanet.fi:1472013", "language": null, "element": "identifier", "qualifier": "other", "schema": "dc"}, {"key": "dc.identifier.uri", "value": "https://jyx.jyu.fi/handle/123456789/45604", "language": null, "element": "identifier", "qualifier": "uri", "schema": "dc"}, {"key": "dc.description.abstract", "value": "MAO-B (MAO-B) on yksi amiinien hapetuksesta vastaavista entsyymeist\u00e4. Se vaikuttaa esimerkiksi aivoissa hermosolujen toimintaan s\u00e4\u00e4telem\u00e4ll\u00e4 hermov\u00e4litt\u00e4j\u00e4aineiden pitoisuutta solun sis\u00e4ll\u00e4. MAO-B-inhibiittoreilla voidaan est\u00e4\u00e4 kyseisen entsyymin toimintaa ja t\u00e4ten liiallista amiinien hajotusta, joka voi johtaa muun muassa hermostosairauksiin. T\u00e4ss\u00e4 tutkimuksessa pyrittiin suunnittelemaan ihmisen MAO-B:hen sitoutuvien 3-fenyylikumariineja. Tutkimus jakautui kahteen osaan. Ensimm\u00e4isess\u00e4 osassa tietokonemallinnuksella tietokantoja seulomalla ja l\u00f6ydettyj\u00e4 molekyylej\u00e4 telakoimalla l\u00f6ytyi seitsem\u00e4n uutta molekyyli\u00e4, jotka sis\u00e4lsiv\u00e4t paljon rengasrakenteita ja fluoriryhmi\u00e4. Molekyylit vuorovaikuttivat entsyymin aktiivisessa taskussa erityisesti Cys172 ja Tyr398 tai Tyr435 aminohappojen kanssa. Molekyyleille tehtyjen inhibiitioaktiivisuusmittausten perusteella yhdisteet inhiboivat MAO B:t\u00e4 hyvin ja inhibiitioprosentit vastasivat tietokonemallinnuksen tuloksia. Toisessa osassa tutkittiin testiaineiden vuorovaikutuksia MAO-B:n kanssa niin tietokonemallinnuksella kuin spektrofotometrisill\u00e4 in vitro mittauksilla. Testiaineiden kumariinirakenteessa tai siihen kiinnittyneess\u00e4 3-fenyylirenkaassa oli sitoutuneena metoksi- tai hydroksyylisubstituentteja. In vitro mittauksissa k\u00e4ytetyill\u00e4 konsentraatioilla metoksisubstituoiduilla 3-fenyylikumariineilla saatiin l\u00e4hes 100 %:nen MAO-B:n inhibiitio. Hydroksyylisubstituoidut yhdisteet sen sijaan inhiboivat noin 80 ja 40 %:sti. MAO-A:ta vastaan havaittiin vain matalaa inhibiitiota, mik\u00e4 teki yhdisteist\u00e4 selektiivisi\u00e4 MAO-B:t\u00e4 kohtaan. K\u00e4ytettyjen substituenttien vaikutus aktiivisuuteen on my\u00f6s yhtenev\u00e4 aiempien tutkimusten kanssa, joissa metoksiryhm\u00e4n on havaittu olevan hydroksyyliryhm\u00e4\u00e4 lupaavampi. Suunniteltujen molekyylien korkea inhibiitioaktiivisuus yhdess\u00e4 laskennallisten tulosten kanssa osoittaa menetelmien ja suunniteltujen molekyylien hy\u00f6dyllisyyden. Kehitetty\u00e4 molekyylisarjaa voidaan jatkossa hy\u00f6dynt\u00e4\u00e4 uusien MAO-B:n kautta vaikuttavien l\u00e4\u00e4kkeiden, kuten Parkinsonin taudin l\u00e4\u00e4kkeiden, kehityksess\u00e4.", "language": "fi", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.abstract", "value": "Monoamine oxidase B (MAO-B) is part of the enzymes responsible for the oxidative metabolism of certain amines. In the brain it can have an effect on the functions of nerve cells by controlling the neurotransmitter concentrations inside the cell. MAO-B inhibitors can be used to prevent the enzymes activity and thus excessive deamination which could lead to diseases of the nervous system. The aim of this study was to find new 3-phenylcoumarins capable of interacting with human MAO-B. The study was divided into two parts. In the first part computer modelling was used to sort through databases and to dock found molecules. Seven new molecules were found with many ring structures and fluorine substituents. These molecules interacted especially with amino acids Cys172 and Tyr389 or Tyr435 in the active site of the binding pocket of the enzyme. And based on the inhibition activity measurements of these molecules, they succeed in inhibiting MAO-B and their inhibition percentages correlated with the results in computer modelling. In the second part of the experiment eight test compounds were studied with computer modelling and spectrophotometric in vitro studies for their interactions and inhibition activities with MAO-B. The test compounds had methoxy or hydroxyl substituents at the coumarin or 3-phenyl structure. In the in vitro measurements compounds with methoxy substituent showed almost always 100 % MAO-B inhibition. Hydroxyl substituents had only about 80 % and 40 % inhibition. Inhibition against monoamine oxidase A was low making these compound selective inhibitors against MAO-B. These effects on inhibition are in line with the previous studies which show more promise with methoxy than hydroxyl subtituents. The correlation between the computational results and the inhibition activities of the designed molecules shows effectiveness of both the methods and the designed molecules. The molecule series constructed here can be utilized in the future developments of new medicines involving MAO-B, like drugs for the treatment of Parkinson\u2019s disease.", "language": "en", "element": "description", "qualifier": "abstract", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted using Plone Publishing form by Mira Pasanen (mievpasa) on 2015-04-08 07:47:44.712096. Form: Pro gradu -lomake (https://kirjasto.jyu.fi/julkaisut/julkaisulomakkeet/pro-gradu-lomake). JyX data: [jyx_publishing-allowed (fi) =True]", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Submitted by jyx lomake-julkaisija (jyx-julkaisija@noreply.fi) on 2015-04-08T07:47:45Z\nNo. of bitstreams: 2\nURN:NBN:fi:jyu-201504081553.pdf: 2096222 bytes, checksum: 35c174d3fea068d521304ba71b13d96a (MD5)\nlicense.html: 4832 bytes, checksum: 4011b1eeaedec3501821c68db23e9233 (MD5)", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.description.provenance", "value": "Made available in DSpace on 2015-04-08T07:47:45Z (GMT). No. of bitstreams: 2\nURN:NBN:fi:jyu-201504081553.pdf: 2096222 bytes, checksum: 35c174d3fea068d521304ba71b13d96a (MD5)\nlicense.html: 4832 bytes, checksum: 4011b1eeaedec3501821c68db23e9233 (MD5)\n Previous issue date: 2015", "language": "en", "element": "description", "qualifier": "provenance", "schema": "dc"}, {"key": "dc.format.extent", "value": "1 verkkoaineisto (42 sivua)", "language": null, "element": "format", "qualifier": "extent", "schema": "dc"}, {"key": "dc.format.mimetype", "value": "application/pdf", "language": null, "element": "format", "qualifier": "mimetype", "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": "monoamiinioksidaasi", "language": null, "element": "subject", "qualifier": "other", "schema": "dc"}, {"key": "dc.title", "value": "Uusien alatyyppivalikoivien monoamiinioksidaasi B -inhibiittoreiden suunnittelu", "language": null, "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-201504081553", "language": null, "element": "identifier", "qualifier": "urn", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Pro gradu -tutkielma", "language": "fi", "element": "type", "qualifier": "ontasot", "schema": "dc"}, {"key": "dc.type.ontasot", "value": "Master\u2019s thesis", "language": "en", "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": "University of Jyv\u00e4skyl\u00e4", "language": "en", "element": "contributor", "qualifier": "organization", "schema": "dc"}, {"key": "dc.contributor.organization", "value": "Jyv\u00e4skyl\u00e4n yliopisto", "language": "fi", "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": "dc.date.updated", "value": "2015-04-08T07:47:46Z", "language": null, "element": "date", "qualifier": "updated", "schema": "dc"}, {"key": "yvv.contractresearch.funding", "value": "0", "language": null, "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": "fi", "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": null, "element": "subject", "qualifier": "oppiainekoodi", "schema": "dc"}, {"key": "dc.subject.yso", "value": "kumariinit", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.subject.yso", "value": "Parkinsonin tauti", "language": null, "element": "subject", "qualifier": "yso", "schema": "dc"}, {"key": "dc.format.content", "value": "fulltext", "language": null, "element": "format", "qualifier": "content", "schema": "dc"}, {"key": "dc.rights.url", "value": "https://rightsstatements.org/page/InC/1.0/", "language": null, "element": "rights", "qualifier": "url", "schema": "dc"}, {"key": "dc.type.okm", "value": "G2", "language": null, "element": "type", "qualifier": "okm", "schema": "dc"}]
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