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dc.contributor.authorEhrit, J.*
dc.contributor.authorKeys, T.G.*
dc.contributor.authorSutherland, Mark*
dc.contributor.authorWolf, S.*
dc.contributor.authorMeier, C.*
dc.contributor.authorFalconer, Robert A.*
dc.contributor.authorGerardy-Schahn, R.*
dc.date.accessioned2017-05-25T13:24:32Z
dc.date.available2017-05-25T13:24:32Z
dc.date.issued2017
dc.identifier.citationEhrit J, Keys TG, Sutherland M et al (2017) Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen. ChemBioChem. 18(13): 1332-1337.
dc.identifier.urihttp://hdl.handle.net/10454/12040
dc.descriptionYes
dc.description.abstractα2,8-Linked polysialic acid (polySia) is an oncofoetal antigen with high abundance during embryonic development. It reappears in malignant tumours of neuroendocrine origin. Two polysialyltransferases (polySTs) ST8SiaII and IV are responsible for polySia biosynthesis. During development, both enzymes are essential to control polySia expression. However, in tumours ST8SiaII is the prevalent enzyme. Consequently, ST8SiaII is an attractive target for novel cancer therapeutics. A major challenge is the high structural and functional conservation of ST8SiaII and -IV. An assay system that enables differential testing of ST8SiaII and -IV would be of high value to search for specific inhibitors. Here we exploited the different modes of acceptor recognition and elongation for this purpose. With DMB-DP3 and DMB-DP12 (fluorescently labelled sialic acid oligomers with a degree of polymerisation of 3 and 12, respectively) we identified stark differences between the two enzymes. The new acceptors enabled the simple comparative testing of the polyST initial transfer rate for a series of CMP-activated and N-substituted sialic acid derivatives. Of these derivatives, the non-transferable CMP-Neu5Cyclo was found to be a new, competitive ST8SiaII inhibitor.
dc.language.isoen
dc.rights© 2017 Wiley. This is the peer-reviewed version of the following article: Ehrit J, Keys TG, Sutherland M et al (2017) Exploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen. Accepted for publication, which has been published in final form at http://dx.doi.org/10.1002/cbic.201700157. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self- Archiving.
dc.subjectFluorescent probes
dc.subjectInhibitors
dc.subjectPolysialic acid
dc.subjectPolysialyltransferase
dc.subjectSialic acid
dc.titleExploring and Exploiting Acceptor Preferences of the Human Polysialyltransferases as a Basis for an Inhibitor Screen
dc.status.refereedYes
dc.date.Accepted2017-05-04
dc.date.application2017-05-24
dc.typeArticle
dc.type.versionAccepted manuscript
dc.identifier.doihttps://doi.org/10.1002/cbic.201700157
dc.rights.licenseUnspecified
refterms.dateFOA2018-05-25T00:00:00Z
dc.openaccess.statusopenAccess


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