Structure-activity relationships of non-opioid [des-Arg7]-dynorphin A analogues for bradykinin receptors

Yeon Sun Lee; David Rankin; Sara M. Hall; Cyf Ramos-Colon; Jose Juan Ortiz; Robert Kupp; Frank Porreca; Josephine Lai; Victor J Hruby

doi:10.1016/j.bmcl.2014.09.033

Structure-activity relationships of non-opioid [des-Arg⁷]-dynorphin A analogues for bradykinin receptors

Yeon Sun Lee, David Rankin, Sara M. Hall, Cyf Ramos-Colon, Jose Juan Ortiz, Robert Kupp, Frank Porreca, Josephine Lai, Victor J Hruby

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

In our earlier studies, bradykinin receptors (BRs) were identified as a potential target for the neuroexcitatory effects of dynorphin A (Dyn A) in the central nervous system (CNS), and [des-Arg⁷]-Dyn A-(4-11) (6) was discovered as a lead ligand to modulate Dyn A-(2-13) induced neuroexcitatory effects in the CNS as an antagonist. In an effort to gain insights into key structural features of the Dyn A for the BRs, we pursued further structure-activity relationships (SAR) study on the [des-Arg⁷]-Dyn A analogs and confirmed that all of the [des-Arg⁷]-Dyn A analogues showed good binding affinities at the BRs.

Original language	English (US)
Pages (from-to)	4976-4979
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	24
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2014.09.033
State	Published - Nov 1 2014

Keywords

Bradykinin receptors
Chronic pain
Non-opioid dynorphin A
Structure-activity relationship
pH sensitivity

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2014.09.033

Cite this

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title = "Structure-activity relationships of non-opioid [des-Arg7]-dynorphin A analogues for bradykinin receptors",

abstract = "In our earlier studies, bradykinin receptors (BRs) were identified as a potential target for the neuroexcitatory effects of dynorphin A (Dyn A) in the central nervous system (CNS), and [des-Arg7]-Dyn A-(4-11) (6) was discovered as a lead ligand to modulate Dyn A-(2-13) induced neuroexcitatory effects in the CNS as an antagonist. In an effort to gain insights into key structural features of the Dyn A for the BRs, we pursued further structure-activity relationships (SAR) study on the [des-Arg7]-Dyn A analogs and confirmed that all of the [des-Arg7]-Dyn A analogues showed good binding affinities at the BRs.",

keywords = "Bradykinin receptors, Chronic pain, Non-opioid dynorphin A, Structure-activity relationship, pH sensitivity",

author = "Lee, {Yeon Sun} and David Rankin and Hall, {Sara M.} and Cyf Ramos-Colon and Ortiz, {Jose Juan} and Robert Kupp and Frank Porreca and Josephine Lai and Hruby, {Victor J}",

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AU - Lee, Yeon Sun

AU - Rankin, David

AU - Hall, Sara M.

AU - Ramos-Colon, Cyf

AU - Ortiz, Jose Juan

AU - Kupp, Robert

AU - Porreca, Frank

AU - Lai, Josephine

AU - Hruby, Victor J

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AB - In our earlier studies, bradykinin receptors (BRs) were identified as a potential target for the neuroexcitatory effects of dynorphin A (Dyn A) in the central nervous system (CNS), and [des-Arg7]-Dyn A-(4-11) (6) was discovered as a lead ligand to modulate Dyn A-(2-13) induced neuroexcitatory effects in the CNS as an antagonist. In an effort to gain insights into key structural features of the Dyn A for the BRs, we pursued further structure-activity relationships (SAR) study on the [des-Arg7]-Dyn A analogs and confirmed that all of the [des-Arg7]-Dyn A analogues showed good binding affinities at the BRs.

KW - Bradykinin receptors

KW - Chronic pain

KW - Non-opioid dynorphin A

KW - Structure-activity relationship

KW - pH sensitivity

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