Evidence map›Paper›PMID 40183236›Full record

ArticleChembiochem : a European journal of chemical biology2025

Macrocycles of Saxitoxin: Insights into the Structure of Zetekitoxin AB.

Wenyuan Li, Srinivas R Paladugu, Jordan P Liles, Manju Karthikeyan, Kevin Chase, Shrinivasan Raghuraman, Matthew S Sigman, Ryan E Looper

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Chembiochem : a European journal of chemical biology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing 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

3 citing papers in PubMed.

  1. Review
  2. Article
  3. 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

8 authors.

Wenyuan LiDepartment of Chemistry, University of Utah, Salt Lake City, UT, 84102, USA.ORCID https://orcid.org/0009-0001-9595-7301
Srinivas R PaladuguDepartment of Chemistry, University of Utah, Salt Lake City, UT, 84102, USA.
Jordan P LilesDepartment of Chemistry, University of Utah, Salt Lake City, UT, 84102, USA.
Manju KarthikeyanSchool of Biological Sciences, University of Utah, Salt Lake City, UT, 84102, USA.
Kevin ChaseSchool of Biological Sciences, University of Utah, Salt Lake City, UT, 84102, USA.
Shrinivasan RaghuramanSchool of Biological Sciences, University of Utah, Salt Lake City, UT, 84102, USA.
Matthew S SigmanDepartment of Chemistry, University of Utah, Salt Lake City, UT, 84102, USA.
Ryan E LooperDepartment of Chemistry, University of Utah, Salt Lake City, UT, 84102, USA.ORCID https://orcid.org/0000-0003-1626-1363

Funding

Pd-Catalyzed Olefin Functionalization Reactions for Organic SynthesisR01GM063540 · NIGMS · UNIVERSITY OF UTAH · PI SIGMAN, MATTHEW S · 2002 to 2019
$5.3M
EXTRAMURAL RESEARCH FACILITIES CONSTRUCTIONC06RR017539 · NCRR · UNIVERSITY OF UTAH · PI PUGMIRE, RONALD J · 2003 to 2003
$3.8M
Data Science Guided Organic Reaction DevelopmentR35GM136271 · NIGMS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI MATTHEW S SIGMAN · 2020 to 2026
$3.5M
Synthetic and biological investigations of 2-aminoimidazole derived natural products.R01GM090082 · NIGMS · UNIVERSITY OF UTAH · PI LOOPER, RYAN EDWARD · 2010 to 2019
$2.6M
“Conus venom peptides and their molecular targets: Using pharmaconomics and neuroethology as a framework for discovery”R01GM144719 · NIGMS · UTAH STATE HIGHER EDUCATION SYSTEM--UNIVERSITY OF UTAH · PI OLIVERA, BALDOMERO M, RAGHURAMAN, SHRINIVASAN · 2022 to 2025
$2.5M
A 500MHz NMR Spectrometer with AutomationS10OD025241 · OD · UNIVERSITY OF UTAH · PI FLYNN, PETER F · 2018 to 2018
$600k
NCRR NIH HHS C06 RR017539NIGMS NIH HHS R01 GM063540NIGMS NIH HHS R01 GM090082NIGMS NIH HHS R01GM090082-A1NIGMS NIH HHS R01 GM144719NIGMS NIH HHS R01GM144719NIGMS NIH HHS R35 GM136271NIH HHS 1C06RR017539-01A1NIH HHS 1S10OD25241-01NIH HHS 3R01GM063540-17W1NIH HHS S10 OD025241
6 · The paper itself

Abstract

Zeteketoxin AB is the only macrocyclic member of the bis-guanidinium ion toxins, and the only member reported to be more potent than the parent (+)-saxitoxin. A rationale for this exquisite potency remains difficult to develop due to the scarcity of natural material and a lack of consensus around the specific structure of the toxin itself. A strategy is reported, leveraging an intramolecular Michael addition to forge macrocycles bridging the saxitoxin core, mimicking the proposed structure of zetekitoxin AB. Intriguingly, these analogs do not form a hydrate at C12. Experimental and computational studies suggest that a macrocyclic framework destabilizes the hydrate, casting doubt on the presence of a macrocycle in zetekitoxin. Preliminary activity screening utilizing calcium imaging-based constellation pharmacology demonstrates several analogs to have potent pharmacological activity similar to (+)-saxitoxin despite the lack of the C12 hydrated ketone.

Indexed as

Macrocyclic CompoundsSaxitoxinAnimalsMolecular StructureMacrocyclic CompoundsSaxitoxinguanidineinhibitorsion channelsnatural productstoxins

Identifiers

PMID40183236
PMCPMC12118334

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.