Type and location of fluorescent probes incorporated into the potent mu-opioid peptide [Dmt1]DALDA affect potency, receptor selectivity and intrinsic efficacy*

2005 ◽  
Vol 65 (6) ◽  
pp. 556-563 ◽  
Author(s):  
P.W. Schiller ◽  
I. Berezowska ◽  
G. Weltrowska ◽  
H. Chen ◽  
C. Lemieux ◽  
...  
Keyword(s):  
Fluorescent Probes ◽  
Opioid Peptide ◽  
Receptor Selectivity ◽  
Mu Opioid ◽  
Intrinsic Efficacy

scholarly journals Characterisation of dermorphinATTO488 at recombinant mu opioid peptide receptors

2020 ◽  
Vol 124 (4) ◽  
pp. e206
Author(s):  
D. Giakomidi ◽  
M.F. Bird ◽  
G. Calo ◽  
R. Guerrini ◽  
D.G. Lambert
Keyword(s):  
Opioid Peptide ◽  
Peptide Receptors ◽  
Mu Opioid

New Dimeric Tetrapeptide Enkephalin AnaloguesHydrophilic Spacer Length and Configuration Affects Potency and Receptor Selectivity

1994 ◽  
Vol 49 (3) ◽  
pp. 407-411
Author(s):  
Janusz Stępiński ◽  
S. William Tam
Keyword(s):  
Receptor Binding ◽  
Opioid Peptide ◽  
Binding Activity ◽  
High Potency ◽  
Spacer Length ◽  
Receptor Selectivity ◽  
Receptor Binding Activity ◽  
Peptide Analogues ◽  
Opioid Receptor Binding

AbstractThree new bivalent opioid peptide analogues, 1,3-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-2-propanol, 1,4-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-(2R, 3S)-butanediol and 1,4-di-(tyrosyl-D-alanyl-glycyl-phenylalanylamido)-(2R,3R)-butanediol, were synthesized and tested in vitro for μ, δ and ϰ receptor affinities. They were found to have potent opioid receptor binding activity. The (2S,3S)-butanediol bridge configuration yielded selectivity and high potency for μ and ϰ receptors, while the (2R,3R)-butanediol bridge configuration yielded high potency and selectivity for δ receptors. It thus appears that changes in the length and configuration of the polyhydroxyl bridge in dimeric enkephalin analogues can produce a shift in receptor selectivity profiles and therefore suggest the possibility of developing more selective drugs.

scholarly journals Mechanistic Understanding of Peptide Analogues, DALDA, [Dmt1]DALDA, and KGOP01, Binding to the Mu Opioid Receptor

Molecules ◽  
2020 ◽  
Vol 25 (9) ◽  
pp. 2087 ◽  
Author(s):  
Maria Dumitrascuta ◽  
Marcel Bermudez ◽  
Steven Ballet ◽  
Gerhard Wolber ◽  
Mariana Spetea
Keyword(s):  
Molecular Docking ◽  
Opioid Receptor ◽  
Rank Order ◽  
Opioid Peptide ◽  
Mu Opioid Receptor ◽  
In Vitro Assays ◽  
Peptide Ligand ◽  
Mu Opioid ◽  
Peptide Analogues

The mu opioid receptor (MOR) is the primary target for analgesia of endogenous opioid peptides, alkaloids, synthetic small molecules with diverse scaffolds, and peptidomimetics. Peptide-based opioids are viewed as potential analgesics with reduced side effects and have received constant scientific interest over the years. This study focuses on three potent peptide and peptidomimetic MOR agonists, DALDA, [Dmt1]DALDA, and KGOP01, and the prototypical peptide MOR agonist DAMGO. We present the first molecular modeling study and structure–activity relationships aided by in vitro assays and molecular docking of the opioid peptide analogues, in order to gain insight into their mode of binding to the MOR. In vitro binding and functional assays revealed the same rank order with KGOP01 > [Dmt1]DALDA > DAMGO > DALDA for both binding and MOR activation. Using molecular docking at the MOR and three-dimensional interaction pattern analysis, we have rationalized the experimental outcomes and highlighted key amino acid residues responsible for agonist binding to the MOR. The Dmt (2′,6′-dimethyl-L-Tyr) moiety of [Dmt1]DALDA and KGOP01 was found to represent the driving force for their high potency and agonist activity at the MOR. These findings contribute to a deeper understanding of MOR function and flexible peptide ligand–MOR interactions, that are of significant relevance for the future design of opioid peptide-based analgesics.

scholarly journals Differential Analgesic Effects of a Mu-Opioid Peptide, [Dmt1]DALDA, and Morphine

Pharmacology ◽  
2009 ◽  
Vol 83 (1) ◽  
pp. 33-37 ◽  
Author(s):  
Megumi Shimoyama ◽  
Hazel H. Szeto ◽  
Peter W. Schiller ◽  
Yugo Tagaito ◽  
Hideyuki Tokairin ◽  
...  
Keyword(s):  
Opioid Peptide ◽  
Mu Opioid ◽  
Analgesic Effects

Conformational restriction of the phenylalanine residue in a cyclic opioid peptide analog: effects on receptor selectivity and stereospecificity

1991 ◽  
Vol 34 (10) ◽  
pp. 3125-3132 ◽  
Author(s):  
Peter W. Schiller ◽  
Grazyna Weltrowska ◽  
Nguyen Thi Mai Dung ◽  
Carole Lemieux ◽  
Nga N. Chung ◽  
...  
Keyword(s):  
Opioid Peptide ◽  
Conformational Restriction ◽  
Receptor Selectivity ◽  
Peptide Analog ◽  
Phenylalanine Residue

scholarly journals An endogenous opioid circuit determines state-dependent appetitive behavior

2021 ◽  
Author(s):  
Daniel C. Castro ◽  
Corinna S. Oswell ◽  
Eric T. Zhang ◽  
Christian E. Pedersen ◽  
Sean C. Piantadosi ◽  
...  
Keyword(s):  
Nucleus Accumbens ◽  
Opioid Peptide ◽  
Behavioral State ◽  
Endogenous Opioid ◽  
Mu Opioid ◽  
Peptide Receptor ◽  
Appetitive Behavior ◽  
State Dependent ◽  
Selective Modulation ◽  
Necessary And Sufficient

AbstractMu-opioid peptide receptor (MOPR) stimulation alters respiration, analgesia, and reward behavior, and can induce addiction and drug overdose. Despite its evident importance, the endogenous mechanisms for MOPR regulation of appetitive behavior have remained unknown. Here we report that endogenous MOPR regulation of appetitive behavior in mice acts through a specific dorsal raphe to nucleus accumbens projection. MOPR-mediated inhibition of raphe terminals is necessary and sufficient to determine appetitive behavioral state while select enkephalin-containing NAc ensembles are engaged prior to reward consumption, suggesting that local enkephalin release is the source of endogenous MOPR ligand. Selective modulation of NAc enkephalin neurons and CRISPR-Cas9-mediated disruption of enkephalin substantiate this finding. These results isolate a fundamental endogenous opioid circuit for state-dependent appetitive behavior and suggest alternative mechanisms for opiate modulation of reward.

Opioid peptide receptor studies. 14. Stereochemistry determines agonist efficacy and intrinsic efficacy in the [35S]GTP-?-S functional binding assay

Synapse ◽  
2000 ◽  
Vol 39 (1) ◽  
pp. 64-69 ◽  
Author(s):  
Heng Xu ◽  
Akihiro Hashimoto ◽  
Kenner C. Rice ◽  
Arthur E. Jacobson ◽  
James B. Thomas ◽  
...  
Keyword(s):  
Binding Assay ◽  
Opioid Peptide ◽  
Peptide Receptor ◽  
Intrinsic Efficacy
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