Editorial
Introduction to ‘Medicinal Chemistry Small Molecule Probes’
Gemma Nixon, Khondaker Miraz Rahman and John Spencer introduce the RSC Chemical Biology themed collection on ‘Medicinal Chemistry Small Molecule Probes’.
Opinion
Chirality: a key parameter in chemical probes
Chiral compounds are vital as chemical probes. Choosing a wrong enantiomer (mirror image) can be disastrous in a medicinal chemistry programme. Here, a male kingfisher emerges from the water with its “active form” above the surface.
Review Article
Sialic acids in infection and their potential use in detection and protection against pathogens
An overview of sialic acid involvement in infection and exploitation in diagnostics and therapeutics.
Review Article
Antitumour imidazotetrazines: past, present… and future?
Are we there yet? The 40 year quest for a new temozolomide.
Review Article
PROTAC chemical probes for histone deacetylase enzymes
A review on current proteolysis targeting chimeras (PROTACs) as chemical probes for histone deacetylase (HDAC) enzymes.
Review Article
P1 Glutamine isosteres in the design of inhibitors of 3C/3CL protease of human viruses of the Pisoniviricetes class
Viral infections are one of the leading causes of acute morbidity in humans and much endeavour has been made by the synthetic community for the development of drugs to treat associated diseases.
Communication
Virtual screening, identification and in vitro validation of small molecule GDP-mannose dehydrogenase inhibitors
Identification of the first small molecule inhibitor for the guanosine diphosphate mannose dehydrogenase from Pseudomonas aeruginosa.
Paper
Discovery of potent and selective activity-based probes (ABPs) for the deubiquitinating enzyme USP30
IMP-2586 and IMP-2587 are selective and potent small molecule USP30 activity-based probes that engage USP30 rapidly in intact cells.
Paper
Design, synthesis and modelling of photoreactive chemical probes for investigating target engagement of plasmepsin IX and X in Plasmodium falciparum
We report the synthesis and biological profiling of photoreactive chemical probes based on an established plasmepsin X inhibitor scaffold. Maintained antimalarial and recombinant enzyme activity support their use in future chemical proteomic studies.
Paper
A cell-permeable probe for the labelling of a bacterial glycosyltransferase and virulence factor
We report a chemical probe for the fluorescent labelling of the bacterial glycosyltransferase LgtC, a known virulence factor in Haemophilus and Neisseria species, and its application with recombinant protein, cell lysates, and intact cells.
Paper
Red-light modulated ortho-chloro azobenzene photoswitch for peptide stapling via aromatic substitution
Development and proof-of-concept for a photoswitchable peptide staple with the ability to trigger a major change in binding affinity upon visible light irradiation.
Paper
Covalent targeting of non-cysteine residues in PI4KIIIβ
The synthesis and characterisation of fluorosulfate covalent inhibitors of the catalytic lysine, a distal tyrosine or both residues in the lipid kinase PI4KIIIβ is described.
Paper
Kinetic and inhibition studies on human Jumonji-C (JmjC) domain-containing protein 5
Robust mass spectrometry-based assays are reported which monitor catalysis of the 2-oxoglutarate-dependent oxygenase Jumonji-C domain-containing protein 5 (JMJD5). The assays have been applied to both kinetic and inhibition studies.
About this collection
We are pleased to present this themed collection Guest Edited by Prof. John Spencer (University of Sussex, UK), Dr Gemma Nixon (University of Liverpool, UK), and Prof. Miraz Rahman (King’s College London, UK).
This themed collection features contributions which investigate general medicinal chemistry, chemical probes for imaging, proteomics, protacs, fragment-based drug discovery, covalent binders, chemical tools for protein profiling and activity modulation, and natural product inspired medicinal chemistry and chemical biology.