Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors

Yeon Sun Lee; Sara M. Hall; Cyf Ramos-Colon; Michael Remesic; Lindsay Lebaron; Ann Nguyen; David Rankin; Frank Porreca; Josephine Lai; Victor J. Hruby

doi:10.1016/j.bmcl.2014.11.026

Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors

Yeon Sun Lee, Sara M. Hall, Cyf Ramos-Colon, Michael Remesic, Lindsay Lebaron, Ann Nguyen, David Rankin, Frank Porreca, Josephine Lai, Victor J. Hruby

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

9 Scopus citations

Abstract

It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg⁷]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals. We have pursued further modification on the [des-Arg⁷]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.

Original language	English (US)
Pages (from-to)	30-33
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	25
Issue number	1
DOIs	https://doi.org/10.1016/j.bmcl.2014.11.026
State	Published - Jan 1 2015

Keywords

Amphipathicity
Anti-hyperalgesic effect
Bradykinin receptors
Dynorphin
Non-opioid

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2014.11.026

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title = "Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors",

abstract = "It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg7]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using na{\"i}ve or injured animals. We have pursued further modification on the [des-Arg7]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.",

keywords = "Amphipathicity, Anti-hyperalgesic effect, Bradykinin receptors, Dynorphin, Non-opioid",

author = "Lee, {Yeon Sun} and Hall, {Sara M.} and Cyf Ramos-Colon and Michael Remesic and Lindsay Lebaron and Ann Nguyen and David Rankin and Frank Porreca and Josephine Lai and Hruby, {Victor J.}",

note = "Funding Information: This work has been supported by U.S. Public Health Services , NIH , and NIDA P01DA006284 and R01DA013449 . Publisher Copyright: {\textcopyright} 2014 Elsevier Ltd. All rights reserved.",

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AU - Lee, Yeon Sun

AU - Hall, Sara M.

AU - Ramos-Colon, Cyf

AU - Remesic, Michael

AU - Lebaron, Lindsay

AU - Nguyen, Ann

AU - Rankin, David

AU - Porreca, Frank

AU - Lai, Josephine

AU - Hruby, Victor J.

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Y1 - 2015/1/1

N2 - It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg7]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals. We have pursued further modification on the [des-Arg7]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.

AB - It has been shown that under chronic pain or nerve injury conditions, up-regulated dynorphin A (Dyn A) interacts with bradykinin receptors (BRs) to cause hyperalgesia in the spinal cord. Thus BRs antagonist can modulate hyperalgesia by blocking Dyn A's interaction with the BRs in the central nervous system. In our earlier structure-activity relationship (SAR) study, [des-Arg7]-Dyn A-(4-11) 13 was discovered as a minimum pharmacophore for rat brain BRs with its antagonist activity (anti-hyperalgesic effect) in in vivo tests using naïve or injured animals. We have pursued further modification on the [des-Arg7]-Dyn A analogues and identified a key insight into the pharmacophore of the rat brain BRs: amphipathicity.

KW - Amphipathicity

KW - Anti-hyperalgesic effect

KW - Bradykinin receptors

KW - Dynorphin

KW - Non-opioid

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Modification of amphipathic non-opioid dynorphin A analogues for rat brain bradykinin receptors

Abstract

Keywords

ASJC Scopus subject areas

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