Evidence map›Paper›PMID 40168114›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2025

Prolonged signaling of backbone-modified glucagon-like peptide-

Brian P Cary, Marlies V Hager, Zamara Mariam, Rylie K Morris, Matthew J Belousoff, Giuseppe Deganutti, Patrick M Sexton, Denise Wootten, Samuel H Gellman

Abstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
–field-weighted citation impact
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

4 citing papers in PubMed.

  1. Heterochiral peptides reshaping class B1 GPCR agonism.Trends in pharmacological sciences · 2026
    Article
  2. Article
  3. Article
  4. Review
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

9 authors.

Brian P CaryDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.ORCID 0000-0001-9523-2522
Marlies V HagerDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.
Zamara MariamCentre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom.
Rylie K MorrisDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.
Matthew J BelousoffDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Giuseppe DeganuttiCentre for Health and Life Sciences, Coventry University, Coventry CV1 5FB, United Kingdom.ORCID 0000-0001-8780-2986
Patrick M SextonDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.ORCID 0000-0001-8902-2473
Denise WoottenDrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC 3052, Australia.
Samuel H GellmanDepartment of Chemistry, University of Wisconsin-Madison, Madison, WI 53706.ORCID 0000-0001-5617-0058

Funding

BIOTECHNOLOGY TRAINING PROGRAMT32GM008349 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI FOX, BRIAN G · 1989 to 2019
$22.5M
Chemistry-Biology Interface Training ProgramT32GM008505 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI BLACKWELL, HELEN E. · 1993 to 2023
$9.8M
Protein Recognition by Peptidic FoldamersR01GM056414 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI GELLMAN, SAMUEL H. · 1997 to 2023
$6.5M
Processes mediated by polypeptidesR35GM151985 · NIGMS · UNIVERSITY OF WISCONSIN-MADISON · PI SAMUEL H. GELLMAN · 2024 to 2026
$1.8M
Department of Education and Training | Australian Research Council (ARC) IC200100052Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 1150083Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 1154434Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 1155302Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 1184726Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 2025694Federal Government | DHAC | National Health and Medical Research Council (NHMRC) 2026300HHS | NIH | National Institute of General Medical Sciences (NIGMS) GM056414HHS | NIH | National Institute of General Medical Sciences (NIGMS) GM151985NIGMS NIH HHS R01 GM056414NIGMS NIH HHS R35 GM151985NIGMS NIH HHS T32 GM008349NIGMS NIH HHS T32 GM008505NSF | NSF Graduate Research Fellowship Program (GRFP) DGE-1747503
6 · The paper itself

Abstract

Signal duration and subcellular location are emerging as important facets of G protein-coupled receptor (GPCR) function. The glucagon-like peptide-1 receptor (GLP-1R), a clinically relevant class B1 GPCR, stimulates production of the second messenger cyclic adenosine monophosphate (cAMP) upon activation by the native hormone, GLP-1. cAMP production continues after the hormone-receptor complex has been internalized via endocytosis. Here, we report GLP-1 analogues that induce prolonged signaling relative to GLP-1. A single β-amino acid substitution at position 18, with the residue derived from (

Indexed as

Glucagon-Like Peptide 1Glucagon-Like Peptide-1 ReceptorSignal TransductionAnimalsCyclic AMPEndocytosisHEK293 CellsHumansProtein TransportCyclic AMPGLP1R protein, humanGlucagon-Like Peptide 1Glucagon-Like Peptide-1 Receptorcryo-EMdynamicsGLP-1peptidetrafficking

Identifiers

PMID40168114
PMCPMC12002026

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

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.