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Sökning: WFRF:(Danielson U. Helena) > Monitoring drug–tar...

LIBRIS Formathandbok  (Information om MARC21)
FältnamnIndikatorerMetadata
00005909naa a2200577 4500
001oai:DiVA.org:uu-461438
003SwePub
008211214s2022 | |||||||||||000 ||eng|
009oai:prod.swepub.kib.ki.se:150805658
0247 a https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-4614382 URI
0247 a https://doi.org/10.1093/nar/gkac8422 DOI
0247 a http://kipublications.ki.se/Default.aspx?queryparsed=id:1508056582 URI
040 a (SwePub)uud (SwePub)ki
041 a engb eng
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
1001 a Al-Amin, Rasel A.,c Researcher,d 1983-u Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)abdal875
2451 0a Monitoring drug–target interactions through target engagement-mediated amplification on arrays and in situ
264 c 2022-10-03
264 1b Oxford University Press,c 2022
338 a electronic2 rdacarrier
520 a Drugs are designed to bind their target proteins in physiologically relevant tissues and organs to modulate biological functions and elicit desirable clinical outcomes. Information about target engagement at cellular and subcellular resolution is therefore critical for guiding compound optimization in drug discovery, and for probing resistance mechanisms to targeted therapies in clinical samples. We describe a target engagement-mediated amplification (TEMA) technology, where oligonucleotide-conjugated drugs are used to visualize and measure target engagement in situ, amplified via rolling-circle replication of circularized oligonucleotide probes. We illustrate the TEMA technique using dasatinib and gefitinib, two kinase inhibitors with distinct selectivity profiles. In vitro binding by the dasatinib probe to arrays of displayed proteins accurately reproduced known selectivity profiles, while their differential binding to fixed adherent cells agreed with expectations from expression profiles of the cells. We also introduce a proximity ligation variant of TEMA to selectively investigate binding to specific target proteins of interest. This form of the assay serves to improve resolution of binding to on- and off-target proteins. In conclusion, TEMA has the potential to aid in drug development and clinical routine by conferring valuable insights in drug–target interactions at spatial resolution in protein arrays, cells and in tissues.
650 7a MEDICIN OCH HÄLSOVETENSKAPx Medicinsk bioteknologix Medicinsk bioteknologi0 (SwePub)304012 hsv//swe
650 7a MEDICAL AND HEALTH SCIENCESx Medical Biotechnologyx Medical Biotechnology0 (SwePub)304012 hsv//eng
653 a Biology with specialization in Molecular Biotechnology
653 a Biologi med inriktning mot molekylär bioteknik
7001 a Johansson, Larsu Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet4 aut
7001 a Abdurakhmanov, Eldar,d 1977-u Uppsala universitet,Biokemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)eldab338
7001 a Landegren, Nils,d 1986-u Karolinska Institutet,Uppsala universitet,Klinisk diabetologi och metabolism,Center for Molecular Medicine, Department of Medicine (Solna), Science for Life Laboratory, Karolinska Institutet4 aut0 (Swepub:uu)nillan544
7001 a Löf, Lizau Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)lizlo931
7001 a Arngården, Linda,d 1984-u Uppsala universitet,Hematologi4 aut0 (Swepub:uu)linan615
7001 a Blokzijl, Andriesu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)andbl969
7001 a Svensson, Richardu Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ricsv977
7001 a Hammond, Maria,d 1984-u Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)marha169
7001 a Lönn, Peteru Uppsala universitet,Science for Life Laboratory, SciLifeLab,Molekylära verktyg4 aut0 (Swepub:uu)pelon623
7001 a Haybaeck, Johannesu Institute of Pathology, Neuropathology and Molecular Pathology, Medical University of Innsbruck; Diagnostic and Research Institute of Pathology, Medical University of Graz4 aut
7001 a Kamali-Moghaddam, Masoodu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)masookam
7001 a Jenmalm Jensen, Annikau Karolinska Institutet4 aut
7001 a Danielson, U. Helena,c Professor,d 1959-u Uppsala universitet,Biokemi,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)helenads
7001 a Artursson, Peru Uppsala universitet,Institutionen för farmaci,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)perartur
7001 a Lundbäck, Thomasu Department of Medical Biochemistry and Biophysics, Chemical Biology Consortium Sweden (CBCS), Science for Life Laboratory, Karolinska Institutet4 aut
7001 a Landegren, Ulfu Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab4 aut0 (Swepub:uu)ulfland
7102 a Uppsala universitetb Molekylära verktyg4 org
7730 t Nucleic Acids Researchd : Oxford University Pressg 50:22, s. e129-e129q 50:22<e129-e129x 0305-1048x 1362-4962
8564 u https://doi.org/10.1093/nar/gkac842y Fulltext
8564 u https://doi.org/10.21203/rs.3.rs-1109577/v1y Pre-print in full-text
8564 u https://uu.diva-portal.org/smash/get/diva2:1620006/FULLTEXT02.pdfx primaryx Raw objecty fulltext:print
8564 8u https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-461438
8564 8u https://doi.org/10.1093/nar/gkac842
8564 8u http://kipublications.ki.se/Default.aspx?queryparsed=id:150805658

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