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dc.contributor.authorJoshi, Anand Anant
dc.contributor.authorMurray, Thomas F.
dc.contributor.authorAldrich, Jane V.
dc.date.accessioned2018-09-14T18:15:27Z
dc.date.available2018-09-14T18:15:27Z
dc.date.issued2017-05-02
dc.identifier.citationAnand A. Joshi, Thomas F. Murray, Jane V. Aldrich Biopolymers. 2017 Sep; 108(5): 10.1002/bip.23026. doi: 10.1002/bip.23026en_US
dc.identifier.urihttp://hdl.handle.net/1808/26726
dc.description.abstractTo date structure-activity relationship (SAR) studies of the dynorphins (Dyn), endogenous peptides for kappa opioid receptors (KOR), have focused almost exclusively on Dyn A with minimal studies on Dyn B. While both Dyn A and Dyn B have identical N-terminal sequences, their C-terminal sequences differ which could result in differences in pharmacological activity. We performed an alanine scan of the non-glycine residues up through residue 11 of Dyn B amide to explore the role of these side chains in the activity of Dyn B. The analogs were synthesized by fluorenylmethyloxycarbonyl (Fmoc)-based solid phase peptide synthesis and evaluated for their opioid receptor affinities and opioid potency and efficacy at KOR. Similar to Dyn A the N-terminal Tyr1 and Phe4 residues of Dyn B amide are critical for opioid receptor affinity and KOR agonist potency. The basic residues Arg6 and Arg7 contribute to the KOR affinity and agonist potency of Dyn B amide, while Lys10 contributes to the opioid receptor affinity, but not KOR agonist potency, of this peptide. Comparison to the Ala analogs of Dyn A(1-13) suggests that the basic residues in the C-terminus of both peptides contribute to KOR binding, but differences in their relative positions may contribute to the different pharmacological profiles of Dyn A and Dyn B. The other unique C-terminal residues in Dyn B amide also appear to influence the relative affinity of this peptide for KOR. This SAR information may be applied in the design of new Dyn B analogs that could be useful pharmacological toolsen_US
dc.publisherAmerican Peptide Societyen_US
dc.subjectDynorphin Ben_US
dc.subjectAlanine scanen_US
dc.subjectKappa opioid receptoren_US
dc.subjectStructure-activity relationshipsen_US
dc.subjectC-terminal basic residuesen_US
dc.titleAlanine scan of the opioid peptide dynorphin B amideen_US
dc.typeArticleen_US
kusw.kuauthorJoshi, Anand A.
dc.identifier.doihttps://doi.org/10.1002/bip.23026en_US
kusw.oaversionScholarly/refereed, publisher versionen_US
kusw.oapolicyThis item meets KU Open Access policy criteria.en_US
dc.identifier.pmidPMC6003702en_US
dc.rights.accessrightsopenAccessen_US


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