ArticleChemical biology & drug design2014
Crystallographic fragment-based drug discovery: use of a brominated fragment library targeting HIV protease.
Article in Chemical biology & drug design, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed.
- Subtype-Specific HIV-1 Protease and the Role of Hinge and Flap Dynamics in Drug Resistance: A Subtype C Narrative.Viruses · 2025Review
- Specific radiation damage to halogenated inhibitors and ligands in protein-ligand crystal structures.Journal of applied crystallography · 2024Article
- Targeting the conserved active site of splicing machines with specific and selective small molecule modulators.Nature communications · 2024Article
- High-confidence placement of low-occupancy fragments into electron density using the anomalous signal of sulfur and halogen atoms.Acta crystallographica. Section D, Structural biology · 2024Article
- Development of Allosteric NIK Ligands from Fragment-Based NMR Screening.ACS medicinal chemistry letters · 2023Article
- In Vitro and In Silico Antiviral Activity of Di-Halogenated Compounds Derived from L-Tyrosine against Human Immunodeficiency Virus 1 (HIV-1).Current issues in molecular biology · 2023Article
- High-Confidence Placement of Fragments into Electron Density Using Anomalous Diffraction-A Case Study Using Hits Targeting SARS-CoV-2 Non-Structural Protein 1.International journal of molecular sciences · 2023Article
- Halo Library, a Tool for Rapid Identification of Ligand Binding Sites on Proteins Using Crystallographic Fragment Screening.Journal of medicinal chemistry · 2023Article
- Implications of Fragment-Based Drug Discovery in Tuberculosis and HIV.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Elasticity-Associated Functionality and Inhibition of the HIV Protease.Advances in experimental medicine and biology · 2022Article
- Fragment-Based Discovery of Novel Allosteric MEK1 Binders.ACS medicinal chemistry letters · 2021Article
- A Novel Bromine-Containing Paroxetine Analogue Provides Mechanistic Clues for Binding Ambiguity at the Central Primary Binding Site of the Serotonin Transporter.ACS chemical neuroscience · 2019Article
- Proteases: Pivot Points in Functional Proteomics.Methods in molecular biology (Clifton, N.J.) · 2019Review
- Flap-site Fragment Restores Back Wild-type Behaviour in Resistant Form of HIV Protease.Molecular informatics · 2018Article
- Contemporary Use of Anomalous Diffraction in Biomolecular Structure Analysis.Methods in molecular biology (Clifton, N.J.) · 2017Review
- A Modified P1 Moiety Enhances In Vitro Antiviral Activity against Various Multidrug-Resistant HIV-1 Variants and In Vitro Central Nervous System Penetration Properties of a Novel Nonpeptidic Protease Inhibitor, GRL-10413.Antimicrobial agents and chemotherapy · 2016Article
- Developing HIV-1 Protease Inhibitors through Stereospecific Reactions in Protein Crystals.Molecules (Basel, Switzerland) · 2016Article
- Structures of endothiapepsin-fragment complexes from crystallographic fragment screening using a novel, diverse and affordable 96-compound fragment library.Acta crystallographica. Section F, Structural biology communications · 2016Article
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9 authors.
Funding
Abstract
A library of 68 brominated fragments was screened against a new crystal form of inhibited HIV-1 protease in order to probe surface sites in soaking experiments. Often, fragments are weak binders with partial occupancy, resulting in weak, difficult-to-fit electron density. The use of a brominated fragment library addresses this challenge, as bromine can be located unequivocally via anomalous scattering. Data collection was carried out in an automated fashion using AutoDrug at SSRL. Novel hits were identified in the known surface sites: 3-bromo-2,6-dimethoxybenzoic acid (Br6) in the flap site and 1-bromo-2-naphthoic acid (Br27) in the exosite, expanding the chemistry of known fragments for development of higher affinity potential allosteric inhibitors. At the same time, mapping the binding sites of a number of weaker binding Br-fragments provides further insight into the nature of these surface pockets.
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