Evidence map›Paper›PMID 39029338›Full record

ArticleEuropean journal of medicinal chemistry2024

Synthesis and evaluation of (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate analogs as competitive partial agonists of butyrophilin 3A1.

Rohit Singh, Sarita Rani, Yiming Jin, Chia-Hung Christine Hsiao, Andrew J Wiemer

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European journal of medicinal chemistry, 2024. 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
–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

1 citing paper in PubMed.

  1. Investigation of structural and dynamic properties of the Butyrophilin BTN3A1/BTN2A1 cytoplasmic complex byFASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025
    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.

Rohit SinghDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269-3092, United States; Department of Pharmaceutical Sciences, School of Health Sciences & Technology, Dr. Vishwanath Karad, MIT-World Peace University, Pune, 411038, India.
Sarita RaniDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269-3092, United States.
Yiming JinDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269-3092, United States.
Chia-Hung Christine HsiaoDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269-3092, United States.
Andrew J WiemerDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, Connecticut, 06269-3092, United States; Institute for Systems Genomics, University of Connecticut, Storrs, Connecticut, 06269-3092, United States. Electronic address: andrew.wiemer@uconn.edu.

Funding

Role of immune modulating butyrophilins in gamma delta T cell activationR01AI150869 · NIAID · UNIVERSITY OF CONNECTICUT STORRS · PI VINOGRADOVA, OLGA, WIEMER, ANDREW J · 2020 to 2024
$2.0M
Synthesis and evaluation of BTN3A1 ligands for cancer immunotherapyR01CA266138 · NCI · UNIVERSITY OF CONNECTICUT STORRS · PI ANDREW J WIEMER · 2022 to 2026
$1.8M
Development of pHLIP-phosphoantigen conjugates for lymphoma therapyR21CA273042 · NCI · UNIVERSITY OF CONNECTICUT STORRS · PI BAHAL, RAMAN, WIEMER, ANDREW J · 2023 to 2024
$403k
NCI NIH HHS R01 CA266138NCI NIH HHS R21 CA273042NIAID NIH HHS R01 AI150869
6 · The paper itself

Abstract

Phosphoantigens (pAgs) induce conformational changes after binding to the intracellular region of BTN3A1 which result in its clustering with BTN2A1, forming an activating ligand for the Vγ9Vδ2 T cell receptor. Here, we designed a small panel of bulky analogs of the prototypical pAg (E)-4-hydroxy-3-methyl-but-2-enyl diphosphate (HMBPP) that contain an aromatic ring attached to the C-3 position in place of methyl group. These compounds bind with high affinity to BTN3A1 but fail to fully support its interaction with BTN2A1 and only partially trigger T cell activation relative to HMBPP. Furthermore, they can compete with HMBPP for cellular binding to BTN3A1 and reduce the cellular response to HMBPP, a classic partial agonist phenotype. Trifluoromethyl analog 6e was the weakest agonist but the strongest inhibitor of HMBPP ELISA response. Our study provides a rationale for the mode of action of pAg-induced γδ T cell activation and provides insights into other naturally occurring BTN proteins and their respective ligands.

Indexed as

ButyrophilinsOrganophosphorus CompoundsAntigens, CDDose-Response Relationship, DrugHumansLymphocyte ActivationMolecular StructureOrganophosphatesStructure-Activity RelationshipT-Lymphocytes4-hydroxy-3-methyl-2-butenyl diphosphateAntigens, CDBTN3A1 protein, humanButyrophilins(E)-4-hydroxy-3-methylbut-2-enyl diphosphateOrganophosphatesOrganophosphorus CompoundsButyrophilinDiphosphateGammadeltaHMBPPPhosphoantigenγδ T cells

Identifiers

PMID39029338
PMCPMC11323222

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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.