Evidence map›Paper›PMID 32217097›Full record

ArticleBiochemical pharmacology2020

Rational development of a high-affinity secretin receptor antagonist.

Maoqing Dong, Kaleeckal G Harikumar, Sweta R Raval, Juliana E Milburn, Carolyn Clark, Rafael Alcala-Torano, Juan C Mobarec, Christopher A Reynolds, Giovanna Ghirlanda, Arthur Christopoulos and 3 more

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

Article in Biochemical pharmacology, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.7field-weighted citation impact, top 36% 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

6 citing papers in PubMed, 12 citations in OpenAlex.

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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

13 authors at 4 institutions in 3 countries.

Maoqing DongDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, United States.
Kaleeckal G HarikumarDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, United States.
Sweta R RavalDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, United States.
Juliana E MilburnDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, United States.
Carolyn ClarkSchool of Molecular Sciences, Arizona State University, Tempe, AZ 85281, United States.
Rafael Alcala-ToranoSchool of Molecular Sciences, Arizona State University, Tempe, AZ 85281, United States.
Juan C MobarecDepartment of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK.
Christopher A ReynoldsDepartment of Biological Sciences, University of Essex, Wivenhoe Park, Colchester CO4 3SQ, UK.
Giovanna GhirlandaSchool of Molecular Sciences, Arizona State University, Tempe, AZ 85281, United States.
Arthur ChristopoulosDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052 Victoria, Australia.
Denise WoottenDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052 Victoria, Australia.
Patrick M SextonDrug Discovery Biology and Department of Pharmacology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, 3052 Victoria, Australia.
Laurence J MillerDepartment of Molecular Pharmacology and Experimental Therapeutics, Mayo Clinic, Scottsdale, AZ 85259, United States. Electronic address: miller@mayo.edu.
Mayo Clinic in Arizona · USArizona State University · USMonash University · AUUniversity of Essex · GB

Funding

Molecular basis of activation of the prototypic class B G protein-coupled secretin receptorR01GM132095 · NIGMS · MAYO CLINIC ARIZONA · PI MILLER, LAURENCE J, SEXTON, PATRICK M · 2019 to 2022
$1.5M
Biotechnology and Biological Sciences Research Council BB/M006883/1NIGMS NIH HHS R01 GM132095
6 · The paper itself

Abstract

The secretin receptor is a prototypic class B GPCR with substantial and broad pharmacologic importance. The aim of this project was to develop a high affinity selective antagonist as a new and important pharmacologic tool and to aid stabilization of this receptor in an inactive conformation for ultimate structural characterization. Amino-terminal truncation of the natural 27-residue ligand reduced biological activity, but also markedly reduced binding affinity. This was rationally and experimentally overcome with lactam stabilization of helical structure and with replacement of residues with natural and unnatural amino acids. A key new step in this effort was the replacement of peptide residue Leu

Indexed as

Drug DesignAlanineAmino Acid SequenceAnimalsBinding SitesCHO CellsCricetulusGlucagon-Like Peptide-1 ReceptorHumansHydrophobic and Hydrophilic InteractionsLigandsModels, MolecularPeptidesProtein BindingProtein Conformation, alpha-HelicalReceptors, CalcitoninAlanineGLP1R protein, humanGlucagon-Like Peptide-1 ReceptorLigandsPeptidesReceptors, CalcitoninReceptors, Gastrointestinal HormoneReceptors, G-Protein-CoupledSecretinsecretin receptorAntagonistG protein-coupled receptorSecretinSecretin receptor

Identifiers

PMID32217097
PMCPMC7299832
OpenAlexW3013404124

What OpenQuestion holds

Textmetadata
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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.