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dc.contributor.authorPatkar, Kshitij A.
dc.contributor.authorMurray, Thomas F.
dc.contributor.authorAldrich, Jane V.
dc.date.accessioned2017-04-12T16:27:02Z
dc.date.available2017-04-12T16:27:02Z
dc.date.issued2009-11-12
dc.identifier.citationPatkar, K. A., Murray, T. F., & Aldrich, J. V. (2009). The Effects of C-terminal Modifications on the Opioid Activity of [N-BenzylTyr1]Dynorphin A-(1-11) Analogs. Journal of Medicinal Chemistry, 52(21), 6814–6821. http://doi.org/10.1021/jm900715men_US
dc.identifier.urihttp://hdl.handle.net/1808/23633
dc.description.abstractStructural modifications affecting the efficacy of analogs of the endogenous opioid peptide dynorphin (Dyn) A have focused on the N-terminal “message” sequence, based on the “messageaddress” concept. To test the hypothesis that changes in the C-terminal “address” domain could affect efficacy, modified amino acids and cyclic constraints were incorporated into this region of the partial agonist [N-benzylTyr1]Dyn A-(1-11). Modifications in the C-terminal domain of [NbenzylTyr1] Dyn A-(1-11)NH2 resulted in increased kappa opioid receptor (KOR) affinity for all of the linear analogs, but did not affect the efficacy of these peptides at KOR. Cyclization between positions 5 and 8 yielded [N-benzylTyr1,cyclo(D-Asp5,Dap8)]Dyn A-(1-11)NH2 (13) (Patkar et al. J. Med. Chem. 2005, 48, 4500-4503) with high selectivity for KOR. In contrast to the linear peptides, this peptide exhibits negligible efficacy in the AC assay and is a KOR antagonist. These data are consistent with our hypothesis that appropriate modifications in the “address” domain of Dyn A analogs may affect efficacy.en_US
dc.publisherAmerican Chemicial Societyen_US
dc.rightsThis document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://dx.doi.org/10.1021/jm900715m.en_US
dc.titleThe Effects of C-terminal Modifications on the Opioid Activity of [N-BenzylTyr1]Dynorphin A-(1-11) Analogsen_US
dc.typeArticleen_US
kusw.kuauthorPatkar, Kshitij
kusw.kuauthorAldrich, Jane V.
kusw.kudepartmentMedicinal Chemistryen_US
dc.identifier.doi10.1021/jm900715men_US
kusw.oaversionScholarly/refereed, author accepted manuscripten_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.rights.accessrightsopenAccess


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