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    Alanine scan of the opioid peptide dynorphin B amide

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    Joshi_2017_AlanineScan.pdf (461.5Kb)
    Issue Date
    2017-05-02
    Author
    Joshi, Anand Anant
    Murray, Thomas F.
    Aldrich, Jane V.
    Publisher
    American Peptide Society
    Type
    Article
    Article Version
    Scholarly/refereed, publisher version
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    Abstract
    To 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 tools
    URI
    http://hdl.handle.net/1808/26726
    DOI
    https://doi.org/10.1002/bip.23026
    Collections
    • Medicinal Chemistry Scholarly Works [242]
    Citation
    Anand A. Joshi, Thomas F. Murray, Jane V. Aldrich Biopolymers. 2017 Sep; 108(5): 10.1002/bip.23026. doi: 10.1002/bip.23026

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    KU Libraries
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    785-864-8983

    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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