Evidence map›Paper›PMID 23932788›Full record

ArticleBioorganic & medicinal chemistry letters2013

N-terminal guanidinylation of TIPP (Tyr-Tic-Phe-Phe) peptides results in major changes of the opioid activity profile.

Grazyna Weltrowska, Thi M-D Nguyen, Nga N Chung, Brian C Wilkes, Peter W Schiller

Open access · greenAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
1.0field-weighted citation impact, top 29% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 9 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 1 institution in 1 country.

Grazyna WeltrowskaLaboratory of Chemical Biology and Peptide Research, Clinical Research Institute of Montreal, Montreal, QC, Canada.
Thi M-D Nguyen
Nga N Chung
Brian C Wilkes
Peter W Schiller
Montreal Clinical Research Institute · CA

Funding

DEVELOPMENT OF RECEPTOR-SPECIFIC OPIOID PEPTIDE ANALOGSR01DA004443 · NIDA · CLINICAL RESEARCH INSTITUTE OF MONTREAL · PI SCHILLER, PETER W · 1987 to 2016
$2.0M
DEVELOPMENT OF RECEPTOR SPECIFIC OPIOID PEPTIDE ANALOGSR37DA004443 · NIDA · CLINICAL RESEARCH INSTITUTE OF MONTREAL · PI SCHILLER, PETER W · 1997 to 2003
$621k
CIHR MOP-89716NIDA NIH HHS DA004443NIDA NIH HHS R01 DA004443NIDA NIH HHS R37 DA004443
6 · The paper itself

Abstract

Derivatives of peptides of the TIPP (Tyr-Tic-Phe-Phe; Tic=1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid) family containing a guanidino (Guan) function in place of the N-terminal amino group were synthesized in an effort to improve their blood-brain barrier permeability. Unexpectedly, N-terminal amidination significantly altered the in vitro opioid activity profiles. Guan-analogues of TIPP-related δ opioid antagonists showed δ partial agonist or mixed δ partial agonist/μ partial agonist activity. Guanidinylation of the mixed μ agonist/δ antagonists H-Dmt-Tic-Phe-Phe-NH2 (DIPP-NH2) and H-Dmt-TicΨ[CH2NH]Phe-Phe-NH2 (DIPP-NH2[Ψ]) converted them to mixed μ agonist/δ agonists. A docking study revealed distinct positioning of DIPP-NH2 and Guan-DIPP-NH2 in the δ receptor binding site. Lys(3)-analogues of DIPP-NH2 and DIPP-NH2[Ψ] (guanidinylated or non-guanidinylated) turned out to be mixed μ/κ agonists with δ antagonist-, δ partial agonist- or δ full agonist activity. Compounds with some of the observed mixed opioid activity profiles have therapeutic potential as analgesics with reduced side effects or for treatment of cocaine addiction.

Indexed as

Dose-Response Relationship, DrugGuanidinesModels, MolecularOligopeptidesReceptors, Opioid, deltaStructure-Activity RelationshipTetrahydroisoquinolinesGuanidinesOligopeptidesReceptors, Opioid, deltaTetrahydroisoquinolinestyrosyl-1,2,3,4-tetrahydro-3-isoquinolinecarbonyl-phenylalanyl-phenylalanine1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid1,3-diisopropylcarbodiimide2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate2′,6′-dimethyltyrosine(5α,7α,8β-(−)-N-methyl-N-[7-(1-pyrrolidinyl)-1-oxaspiro[4.5]dec-8-yl]benzeneacetamide6-chloro-1-hydroxybenzotriazoleBBBblood–brain barrierBocCl-HOBtDAMGODICDIPPDIPP-NH(2)DIPP-NH(2)[Ψ]DmtDSLETelectrospray mass spectrometryES-MSGPIGuanguanidinoGuanidinylated opioid peptidesguinea pig ileumHBTUH-Dmt-Tic-Phe-Phe-NH(2)H-Dmt-Tic-Phe-Phe-OHH-Dmt-TicΨ[CH(2)NH]Phe-Phe-NH(2)high performance liquid chromatographyHPLCH-Tyr-D-Ala-Gly-Phe(NMe)-Gly-olH-Tyr-D-Ser-Gly-Phe-Leu-Thr-OHH-Tyr-Tic-Phe-Phe-OHH-Tyr-TicΨ[CH(2)NH]Phe-Phe-OHmouse vas deferensMVDPeptide synthesistert-butyloxycarbonylTicTIPPTIPP[Ψ]U69,593δ Opioid antagonistsδ Partial opioid agonistsμ Opioid agonist/δ opioid agonistsμ Opioid agonist/δ opioid antagonists

Identifiers

PMID23932788
PMCPMC3776131
OpenAlexW1975763156

What OpenQuestion holds

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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.