ArticleChemistry & biology2008
Structure-based dissection of the natural product cyclopentapeptide chitinase inhibitor argifin.
Article in Chemistry & biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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.
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.
Who cites it
28 citing papers in PubMed, 66 citations in OpenAlex.
- Human chitinases and chitinase-like proteins as emerging drug targets - a medicinal chemistry perspective.RSC medicinal chemistry · 2025Review
- A Perspective on the Strategic Application of Deconstruction-Reconstruction in Drug Discovery.Journal of medicinal chemistry · 2025Review
- Resilience in Resistance: The Role of Cell Wall Integrity in Multidrug-Resistant Candida.Journal of fungi (Basel, Switzerland) · 2025Review
- Scaffold repositioning of spiro-acridine derivatives as fungi chitinase inhibitor by target fishing and in vitro studies.Scientific reports · 2023Article
- Conformation-dependent ligand hot spots in the spliceosomal RNA helicase BRR2.Acta crystallographica. Section D, Structural biology · 2023Article
- Cyclodepsipeptides: Isolation from Endophytic Fungi ofMarine drugs · 2022Article
- Discovery of Octahydroisoindolone as a Scaffold for the Selective Inhibition of Chitinase B1 fromMolecules (Basel, Switzerland) · 2021Article
- A Plumieridine-Rich Fraction FromFrontiers in microbiology · 2020Article
- Chitinases: Therapeutic Scaffolds for Allergy and Inflammation.Recent patents on inflammation & allergy drug discovery · 2020Review
- Structural dissection reveals a general mechanistic principle for group II chitinase (ChtII) inhibition.The Journal of biological chemistry · 2019Article
- Exhaustive sampling of the fragment space associated to a molecule leading to the generation of conserved fragments.Chemical biology & drug design · 2018Article
- Label-free NMR-based dissociation kinetics determination.Journal of biomolecular NMR · 2017Article
- When Does Chemical Elaboration Induce a Ligand To Change Its Binding Mode?Journal of medicinal chemistry · 2017Article
- Article
- Lessons from Hot Spot Analysis for Fragment-Based Drug Discovery.Trends in pharmacological sciences · 2015Review
- Ligand deconstruction: Why some fragment binding positions are conserved and others are not.Proceedings of the National Academy of Sciences of the United States of America · 2015Article
- Total synthesis of the putative structure of the proposed Banyasin A.Frontiers in chemistry · 2015Article
- Evolutions in fragment-based drug design: the deconstruction-reconstruction approach.Drug discovery today · 2015Review
- Fully deacetylated chitooligosaccharides act as efficient glycoside hydrolase family 18 chitinase inhibitors.The Journal of biological chemistry · 2014Article
- Observation of the controlled assembly of preclick components in the in situ click chemistry generation of a chitinase inhibitor.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
Corrections and comments
- Commented on by
Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Chitinase inhibitors have chemotherapeutic potential as fungicides, pesticides, and antiasthmatics. Argifin, a natural product cyclopentapeptide, competitively inhibits family 18 chitinases in the nanomolar to micromolar range and shows extensive substrate mimicry. In an attempt to map the active fragments of this large natural product, the cyclopentapeptide was progressively dissected down to four linear peptides and dimethylguanylurea, synthesized using a combination of solution and solid phase peptide synthesis. The peptide fragments inhibit chitinase B1 from Aspergillus fumigatus (AfChiB1), the human chitotriosidase, and chitinase activity in lung homogenates from a murine model of chronic asthma, with potencies ranging from high nanomolar to high micromolar inhibition. X-ray crystallographic analysis of the chitinase-inhibitor complexes revealed that the conformations of the linear peptides were remarkably similar to that of the natural product. Strikingly, the dimethylguanylurea fragment, representing only a quarter of the natural product mass, was found to harbor all significant interactions with the protein and binds with unusually high efficiency. The data provide useful information that could lead to the generation of drug-like, natural product-based chitinase inhibitors.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.