Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2
- Publication Type:
- Journal Article
- Citation:
- ACS Chemical Neuroscience, 2017, 8 (9), pp. 1949 - 1959
- Issue Date:
- 2017-09-20
Open Access
Full metadata record
Field | Value | Language |
---|---|---|
dc.contributor.author | Mostyn, SN | en_US |
dc.contributor.author | Carland, JE | en_US |
dc.contributor.author | Shimmon, S | en_US |
dc.contributor.author | Ryan, RM | en_US |
dc.contributor.author |
Rawling, T |
en_US |
dc.contributor.author | Vandenberg, RJ | en_US |
dc.date.issued | 2017-09-20 | en_US |
dc.identifier.citation | ACS Chemical Neuroscience, 2017, 8 (9), pp. 1949 - 1959 | en_US |
dc.identifier.uri | http://hdl.handle.net/10453/125181 | |
dc.identifier.uri | http://hdl.handle.net/10453/125181 | |
dc.description.abstract | © 2017 American Chemical Society. It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 μM. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors. | en_US |
dc.relation | http://purl.org/au-research/grants/nhmrc/GNT1082570 | |
dc.relation.ispartof | ACS Chemical Neuroscience | en_US |
dc.relation.isbasedon | 10.1021/acschemneuro.7b00105 | en_US |
dc.subject.mesh | Oocytes | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Xenopus laevis | en_US |
dc.subject.mesh | Tritium | en_US |
dc.subject.mesh | Arachidonic Acids | en_US |
dc.subject.mesh | Glycine | en_US |
dc.subject.mesh | RNA, Messenger | en_US |
dc.subject.mesh | Analgesics | en_US |
dc.subject.mesh | Molecular Structure | en_US |
dc.subject.mesh | Membrane Potentials | en_US |
dc.subject.mesh | Micelles | en_US |
dc.subject.mesh | Membrane Transport Modulators | en_US |
dc.subject.mesh | Glycine Plasma Membrane Transport Proteins | en_US |
dc.subject.mesh | Analgesics | en_US |
dc.subject.mesh | Animals | en_US |
dc.subject.mesh | Arachidonic Acids | en_US |
dc.subject.mesh | Glycine | en_US |
dc.subject.mesh | Glycine Plasma Membrane Transport Proteins | en_US |
dc.subject.mesh | Membrane Potentials | en_US |
dc.subject.mesh | Membrane Transport Modulators | en_US |
dc.subject.mesh | Micelles | en_US |
dc.subject.mesh | Molecular Structure | en_US |
dc.subject.mesh | Oocytes | en_US |
dc.subject.mesh | RNA, Messenger | en_US |
dc.subject.mesh | Tritium | en_US |
dc.subject.mesh | Xenopus laevis | en_US |
dc.title | Synthesis and Characterization of Novel Acyl-Glycine Inhibitors of GlyT2 | en_US |
dc.type | Journal Article | |
utslib.description.version | Published | en_US |
utslib.citation.volume | 9 | en_US |
utslib.citation.volume | 8 | en_US |
utslib.for | 0299 Other Physical Sciences | en_US |
utslib.for | 0303 Macromolecular and Materials Chemistry | en_US |
pubs.embargo.period | Not known | en_US |
pubs.organisational-group | /University of Technology Sydney | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science | |
pubs.organisational-group | /University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences | |
utslib.copyright.status | open_access | |
utslib.copyright.embargo | 2018-10-01T00:00:00+1000 | |
pubs.issue | 9 | en_US |
pubs.publication-status | Published | en_US |
pubs.volume | 8 | en_US |
Files in This Item:
Filename | Description | Size | |||
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0C62479F-8877-49E1-AA80-4291C5B7953E am.pdf | Accepted Manuscript Version | 781.87 kB | Adobe PDF |
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Abstract:
© 2017 American Chemical Society. It has been demonstrated previously that the endogenous compound N-arachidonyl-glycine inhibits the glycine transporter GlyT2, stimulates glycinergic neurotransmission, and provides analgesia in animal models of neuropathic and inflammatory pain. However, it is a relatively weak inhibitor with an IC50 of 9 μM and is subject to oxidation via cyclooxygenase, limiting its therapeutic value. In this paper we describe the synthesis and testing of a novel series of monounsaturated C18 and C16 acyl-glycine molecules as inhibitors of the glycine transporter GlyT2. We demonstrate that they are up to 28 fold more potent that N-arachidonyl-glycine with no activity at the closely related GlyT1 transporter at concentrations up to 30 μM. This novel class of compounds show considerable promise as a first generation of GlyT2 transport inhibitors.
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