Evidence map›Paper›PMID 42289774›Full record

ArticleChemistry, an Asian journal2026

Synthesis of a C-2 Functionalized l-Iduronic Acid Derivative as a Candidate Pharmacological Chaperone for MPS II (Hunter Syndrome).

Vaibhavi Nagendra, Shifaza Mohamed, Nicholas W See, Norbert Wimmer, Daniel Neumann, Paul J Trim, Marten Snel, Aidan J Brock, Jack K Clegg, Neha S Gandhi and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chemistry, an Asian journal, 2026. 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. 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

13 authors.

Vaibhavi NagendraSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0009-0002-0328-593X
Shifaza MohamedSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-1143-8986
Nicholas W SeeSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-8038-634X
Norbert WimmerSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-7178-8101
Daniel NeumannChildhood Dementia Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Adelaide, South Australia, Australia.ORCID https://orcid.org/0009-0008-2118-4685
Paul J TrimProteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.ORCID https://orcid.org/0000-0001-8734-3433
Marten SnelProteomics, Metabolomics and MS-Imaging Core Facility, South Australian Health and Medical Research Institute (SAHMRI), Adelaide, South Australia, Australia.ORCID https://orcid.org/0000-0002-8502-7274
Aidan J BrockSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-2763-3321
Jack K CleggSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0002-7140-5596
Neha S GandhiDepartment of Biotechnology and Chemical Engineering, School of Engineering, Faculty of Science, Technology and Architecture, Manipal University, Jaipur, India.ORCID https://orcid.org/0000-0003-3119-6731
Kim M HemsleyChildhood Dementia Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Adelaide, South Australia, Australia.ORCID https://orcid.org/0000-0003-1038-9884
Adeline A LauChildhood Dementia Research Group, College of Medicine and Public Health, Flinders Health and Medical Research Institute (FHMRI), Flinders University, Adelaide, South Australia, Australia.ORCID https://orcid.org/0000-0002-4485-7714
Vito FerroSchool of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, Queensland, Australia.ORCID https://orcid.org/0000-0003-3306-2550

Funding

Australian Research Council DP170104431National MPS Society
6 · The paper itself

Abstract

A C-2 functionalized l-IdoA derivative was designed as a potential pharmacological chaperone for MPS II, and several routes to its synthesis were investigated. Successful synthesis proceeded via an oxidation/Horner-Wadsworth-Emmons sequence, overcoming significant challenges with competing elimination reactions to give alkene derivatives in good overall yields. Catalytic hydrogenation of the double bonds proceeded stereoselectively in high yield to give the desired L-ido-configured products, confirmed by x-ray crystallographic analysis. These were subsequently elaborated to the target dicarboxylate prodrug 1 in good overall yield. Molecular docking studies suggest the parent compound engages with the active site and makes several H-bonding interactions with key active site residues. Target prodrug 1 and known chaperone D2S0 were evaluated against two MPS II cell lines, but neither compound was able to reduce HS substrate levels at the doses tested.

Indexed as

Iduronic AcidProdrugsCell LineCrystallography, X-RayHumansMolecular Docking SimulationIduronic AcidProdrugs

Identifiers

PMID42289774
PMCPMC13265633

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.