Modifications of the cyclic mu receptor selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et): effects on opioid receptor binding and activation
dc.contributor.author | McFadyen, I. J. | en_US |
dc.contributor.author | Ho, Jeffrey C. | en_US |
dc.contributor.author | Mosberg, Henry I. | en_US |
dc.contributor.author | Traynor, John R. | en_US |
dc.date.accessioned | 2010-06-01T18:36:00Z | |
dc.date.available | 2010-06-01T18:36:00Z | |
dc.date.issued | 2000-03 | en_US |
dc.identifier.citation | McFadyen, I.J . ; Ho, J.C . ; Mosberg, H.I . ; Traynor, J.R . (2000). "Modifications of the cyclic mu receptor selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et): effects on opioid receptor binding and activation." The Journal of Peptide Research 55(3): 255-261. <http://hdl.handle.net/2027.42/71802> | en_US |
dc.identifier.issn | 1397-002X | en_US |
dc.identifier.issn | 1399-3011 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/71802 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=10727108&dopt=citation | en_US |
dc.description.abstract | The previously described cyclic mu opioid receptor-selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et) (JOM-6) was modified at residues 1 and 3 by substitution with various natural and synthetic amino acids, and/or by alteration of the cyclic system. Effects on mu and delta opioid receptor binding affinities, and on potencies and efficacies as measured by the [ 35 S]-GTPγS assay, were evaluated. Affinities at mu and delta receptors were not influenced dramatically by substitution of Tyr 1 with conformationally restricted phenolic amino acids. In the [ 35 S]-GTPγS assay, all of the peptides tested exhibited a maximal response comparable with that of fentanyl at the mu opioid receptor, and all showed high potency, in the range0.4–9 nm. However, potency changes did not always correlate with affinity, suggesting that the conformation required for binding and the conformation required for activation of the opioid receptors are different. At the delta opioid receptor, none of the peptides were able to produce a response equivalent to that of the full delta agonist BW 373,U86 and only one had an EC 50 value of less than 100 nm. Lastly, we have identified a peptide, d-Hat-c[d-Cys-Phe-d-Pen]NH 2 (Et), with high potency and > 1000-fold functional selectivity for the mu over delta opioid receptor as measured by the [ 35 S]-GTPγS assay. | en_US |
dc.format.extent | 112027 bytes | |
dc.format.extent | 3109 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.publisher | Munksgaard International Publishers | en_US |
dc.publisher | Blackwell Publishing Ltd | en_US |
dc.rights | Munksgaard International Publishers Ltd, 2000 | en_US |
dc.subject.other | Conformational Restriction | en_US |
dc.subject.other | Cyclic Peptides | en_US |
dc.subject.other | Delta Opioid Receptor | en_US |
dc.subject.other | Mu Opioid Receptor | en_US |
dc.subject.other | Opioid Peptides | en_US |
dc.title | Modifications of the cyclic mu receptor selective tetrapeptide Tyr-c[d-Cys-Phe-d-Pen]NH 2 (Et): effects on opioid receptor binding and activation | en_US |
dc.type | Article | en_US |
dc.subject.hlbsecondlevel | Molecular, Cellular and Developmental Biology | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.identifier.pmid | 10727108 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/71802/1/j.1399-3011.2000.00177.x.pdf | |
dc.identifier.doi | 10.1034/j.1399-3011.2000.00177.x | en_US |
dc.identifier.source | The Journal of Peptide Research | en_US |
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dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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