Synthesis and characterization of 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-labeled fluorescent opioids
dc.contributor.author | Archer, Sydney | en_US |
dc.contributor.author | Medzihradsky, Fedor | en_US |
dc.contributor.author | Seyed-Mozaffari, Ahmad | en_US |
dc.contributor.author | Emmerson, Paul J. | en_US |
dc.date.accessioned | 2006-04-10T15:21:20Z | |
dc.date.available | 2006-04-10T15:21:20Z | |
dc.date.issued | 1992-01-22 | en_US |
dc.identifier.citation | Archer, Sydney, Medzihradsky, Fedor, Seyed-Mozaffari, Ahmad, Emmerson, Paul J. (1992/01/22)."Synthesis and characterization of 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-labeled fluorescent opioids." Biochemical Pharmacology 43(2): 301-306. <http://hdl.handle.net/2027.42/30242> | en_US |
dc.identifier.uri | http://www.sciencedirect.com/science/article/B6T4P-477967D-158/2/7e41a3335cc9db1d590b823035ade1e4 | en_US |
dc.identifier.uri | https://hdl.handle.net/2027.42/30242 | |
dc.identifier.uri | http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=retrieve&db=pubmed&list_uids=1371213&dopt=citation | en_US |
dc.description.abstract | Alkylation of sarcosine with 4-chloro-nitrobenzo-2-oxa-1,3-diazole (NBD-chloride) furnished a fluorescent tag that was coupled with a tetrahydrothebaine derivative and [beta]-naltrexamine, respectively, to yield the fluorescent opioids 7[alpha]-(1R)-1-hydroxy-1-methyl-3-(4-hydroxyphenyl)-propyl]-6,14-endoethenotetrahydrothebaine NBD-sarcosinate (ASM-5-10) and N-cyclopropylmethyl-3-hydroxy-14[beta]-hydroxy-6[beta]-(NBD sarcosinyl)-amino-epoxymorphinan (ASM-5-67). The fluorescence intensity of the novel opioids allowed their detection at subnanomolar concentrations, and was dependent on the polarity of the solvent. Maximum quantum yield was obtained in ethyl acetate and ethanol, and minimal fluorescence in heptane and water. Compounds ASM-5-10 and ASM-5-67 displaced the opioid receptor binding of [3H]Tyr--Ala-Gly-(Me)Phe-Gly-ol in monkey brain membranes with IC50 values of 8.4 and 1.5nM, respectively. Whereas ASM-5-67 bound to [mu], [delta], and [kappa] receptors with comparable affinities, ASM-5-10 was [mu]-selective, with selectivity indices (ratio of respective IC50 values) of 0.04 for both [mu]/[delta] and [mu]/[kappa]. The sodium response ratio in binding revealed a pronounced agonist property of ASM-5-10. Both opioids were lipophilic, with octanol-water partition coefficients (log Papp) of 2.8 (ASM-5-10) and 1.0 (ASM-5-67). ASM-5-10 exhibited particularly strong membrane retention that was not reversible by four washes. Their favorable characteristics in fluorescence, receptor binding, and membrane interaction make these newly developed ligands useful molecular probes to study opioid receptor mechanisms. | en_US |
dc.format.extent | 766991 bytes | |
dc.format.extent | 3118 bytes | |
dc.format.mimetype | application/pdf | |
dc.format.mimetype | text/plain | |
dc.language.iso | en_US | |
dc.publisher | Elsevier | en_US |
dc.title | Synthesis and characterization of 7-nitrobenzo-2-oxa-1,3-diazole (NBD)-labeled fluorescent opioids | en_US |
dc.type | Article | en_US |
dc.rights.robots | IndexNoFollow | en_US |
dc.subject.hlbsecondlevel | Biological Chemistry | en_US |
dc.subject.hlbtoplevel | Science | en_US |
dc.subject.hlbtoplevel | Health Sciences | en_US |
dc.description.peerreviewed | Peer Reviewed | en_US |
dc.contributor.affiliationum | Departments of Biological Chemistry University of Michigan Medical School, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationum | Departments of Pharmacology, University of Michigan Medical School, Ann Arbor, MI 48109, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Chemistry, Cogswell Laboratory, Rensselaer Polytechnic Institute, Troy, NY 12181, U.S.A. | en_US |
dc.contributor.affiliationother | Department of Chemistry, Cogswell Laboratory, Rensselaer Polytechnic Institute, Troy, NY 12181, U.S.A. | en_US |
dc.identifier.pmid | 1371213 | en_US |
dc.description.bitstreamurl | http://deepblue.lib.umich.edu/bitstream/2027.42/30242/1/0000637.pdf | en_US |
dc.identifier.doi | http://dx.doi.org/10.1016/0006-2952(92)90292-Q | en_US |
dc.identifier.source | Biochemical Pharmacology | en_US |
dc.owningcollname | Interdisciplinary and Peer-Reviewed |
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