ArticleACS medicinal chemistry letters2014
C-terminal residue optimization and fragment merging: discovery of a potent Peptide-hybrid inhibitor of dengue protease.
Article in ACS medicinal chemistry letters, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 63 citations in OpenAlex.
- A designed peptide disrupting viral protease cleavage restores cGAS-DNA phase separation and type I interferon responses.PLoS pathogens · 2026Article
- Development of Novel Proline- and Pipecolic Acid-Based Allosteric Inhibitors of Dengue and Zika Virus NS2B/NS3 Protease.Pharmaceuticals (Basel, Switzerland) · 2025Article
- The Inhibition of NS2B/NS3 Protease: A New Therapeutic Opportunity to Treat Dengue and Zika Virus Infection.International journal of molecular sciences · 2024Review
- Designing photoaffinity tool compounds for the investigation of the DENV NS2B-NS3 protease allosteric binding pocket.RSC medicinal chemistry · 2023Article
- Non-Canonical Amino Acids in Analyses of Protease Structure and Function.International journal of molecular sciences · 2023Review
- A competition smFRET assay to study ligand-induced conformational changes of the dengue virus protease.Protein science : a publication of the Protein Society · 2023Article
- Review
- A short survey of dengue protease inhibitor development in the past 6 years (2015-2020) with an emphasis on similarities between DENV and SARS-CoV-2 proteases.Bioorganic & medicinal chemistry · 2021Review
- Targeting the protease of West Nile virus.RSC medicinal chemistry · 2021Review
- Virtual Screening for Potential Inhibitors of Human Hexokinase II for the Development of Anti-Dengue Therapeutics.Biotech (Basel (Switzerland)) · 2020Article
- Peptides targeting dengue viral nonstructural protein 1 inhibit dengue virus production.Scientific reports · 2020Article
- Discovery of Novel Nonpeptidic PAR2 Ligands.ACS medicinal chemistry letters · 2020Article
- Review
- Thioguanine-based DENV-2 NS2B/NS3 protease inhibitors: Virtual screening, synthesis, biological evaluation and molecular modelling.PloS one · 2019Article
- Strategies Towards Protease Inhibitors for Emerging Flaviviruses.Advances in experimental medicine and biology · 2018Review
- Broad-spectrum agents for flaviviral infections: dengue, Zika and beyond.Nature reviews. Drug discovery · 2017Review
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Dengue virus protease is a promising target for the development of antiviral drugs. We describe here a two-step rational optimization that led to the discovery of the potent inhibitor 35 with nanomolar binding affinity at dengue protease serotype 2 (IC50 = 0.6 μM, K i = 0.4 μM). First, a large number of natural and non-natural amino acids were screened at the C-terminal position of the previously reported, canonical peptide sequence (Cap-Arg-Lys-Nle-NH2). Compared to the reference compound 1 (Bz-Arg-Lys-Nle-NH2, IC50 = 13.3 μM), a 4-fold higher inhibitory potential was observed with the incorporation of a C-terminal phenylglycine (compound 9, IC50 = 3.3 μM). Second, we applied fragment merging of 9 with the previously reported thiazolidinedione peptide hybrid 33 (IC50 = 2.5 μM). This approach led to the fusion of two inhibitor-fragments with micromolar affinity into a 20-fold more potent, competitive inhibitor of dengue protease.
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