Themed collection RSC Chemical Biology Transparent Peer Review Collection

An updated outlook on protein lysine methyltransferase-disclosed modulators is presented, reporting their potency, mechanism of action and eventual use in clinical and preclinical studies.

Immune targets and antibodies for cancer immunotherapy are reviewed. Multispecific antibody formats and bioconjugation chemistry to generate them are discussed.

In this mini-review, we summarized the chemical structure, mechanism of action, and metabolism of cyclic peptide drugs approved in the last two decades. We also examined factors important for the development and utilization in clinical situations.

Posttranslational S-fatty acylation (or S-palmitoylation) modulates protein localization and functions, and has been implicated in neurological, metabolic, and infectious diseases, and cancers.

Chemical modulation of the RNA m⁶A demethylase FTO for cancer therapy.

¹⁹F NMR has emerged as a powerful tool in drug discovery, particularly in fragment-based screens.

Mitochondria-targeted drugs inhibit cancer and COVID-19 mechanisms.

Given the therapeutic interest of targeting TDP-43, this review focuses on the current landscape of strategies, ranging from biologics to small molecules, that directly target TDP-43. Regions targeted are shown on the 3D structure of RNA-bound TDP-43.

Overview of the Wnt signaling pathway and targets of Wnt activators.

Various quantitative strategies can be utilized in mass spectrometry (MS)-based proteomic investigations. Here we explore recent applications of quantitative MS-based strategies and the resulting advances in the areas of prostate, pancreatic, breast and ovarian cancer research.

This review details optical detection methods for proximal multi-site phosphorylation, a critical post-translational modification in protein biology.

In vivo imaging has become in recent years an incredible tool to study biological events and has found critical applications in diagnostic medicine.

Heparan sulfate (HS) is a highly sulfated polysaccharide playing essential physiological and pathophysiological roles in the animal kingdom.

Crosslinker-modified nucleic acid probes are promising substitutes for regular oligonucleotide probes in hybridization-based assays, as they allow a more selective and efficient detection of nucleic acid targets and nucleic acid biomarkers.

This review details a brief history of the synthesis and characterization of metabolic chemical reporters used to study glycosylation before describing recent applications and finishing with considerations and limitations of reporter molecules.

This review describes recent efforts towards the modulation of protein–protein interactions in infectious bacteria.

Supramolecular assemblies of small molecules, exhibiting emergent properties, are becoming a new and dynamic molecular platform for biological functions and for developing novel therapeutic approaches.

Alternative DNA structures (including G-quadruplexes and DNA junctions) represent promising targets for combinatorial chemotherapeutic treatments aiming at fostering genomic instability and impeding DNA repair.

The 20S proteasome is a valuable target for the treatment of a number of diseases including cancer, neurodegenerative disease, and parasitic infection.

Interleukin-12 (IL-12) has emerged as an attractive cytokine for cancer therapy because it has direct anti-cancer effects and additionally plays a critical role in enhancing checkpoint inhibitors.

In this review, we give a concise overview of the known biosynthetic princples of class III and IV lanthipeptide synthtases.

An experimentally validated approach for in silico modification of peptide based protein–protein interaction inhibitors is described.

Lipoic acid, an essential cofactor produced in all organisms, diverts octanoic acid from type II fatty acid biosynthesis through a highly specific protein–protein interaction. This study characterizes how different substrates influence this interface to control chain length specificity.

A rationally designed stapled JAZ peptide selectively inhibited MYCs, master-regulators of the jasmonate signaling in Arabidopsis thaliana. It is proposed as a novel chemical tool for the analysis of MYC related jasmonate signaling.

Chemical proteomics and cellular imaging reveal lysosomal trapping of tranylcypromine which can be largely reverted by the addition of lysosomotropic drugs.

A chemical catalyst system enabling high-yielding and comprehensive lysine acetylation of nucleosomal histones was developed as an epigenetics tool.

In AIP-I/IV, single Gly mutation at the thiolactone induces S-to-O acyl shift to yield a corresponding ring-expanded lactone form.

The antibiotic linezolid is an effective herbicide pre- and post-emergence. Making a series of analogues, we partly separated its antibacterial and herbicidal activities, making chloroplast translation a potential new herbicide mode of action.

Ruthenium complexes have emerged as a promising class of compounds for use as photosensitizers in photodynamic therapy. Direct conjugation to aptamers enhances their therapeutic usefulness by conveying specificity to Ru-mediated PDT.

By fragment screening using X-ray crystallography we identified four ligands revealing ligand-binding sites in interfaces between SARS-CoV-2 nsp10 and nsp14/nsp16. The nsp14/10 interaction is weak and therefore could be disrupted by small molecules.

The use of antibodies to target membrane receptors enables specific and potent activation. But antibodies with appropriate specificity can be lacking. We present methods for targeting receptors without target-specific antibodies.

Alkyl chain extension and aryl methylation can be employed to enhance mitochondrial uptake in triphenylphosphonium vectors. Here we compare these complementary strategies and their mitochondrial-targeting effects using a modular synthetic approach.

During infection, Legionella pneumophila translocates hundreds of effectors into host cells. Among these, the Sde family effector SdeC catalyzes atypical ubiquitination of host targets at tyrosine, not only serine, residues.

A small, inherently fluorescent macrocyclic peptide constrained with a bimane-linker is cell permeable, and binds the human sliding clamp protein, PCNA, in a 3₁₀-helical conformation with nanomolar affinity.

The significant improvement in the binding affinity of the stapled peptide to the PSD-95 GK domain is mostly contributed by the reduction in the entropy penalty of the stapled peptide due to the restriction in the α-helical structure by stapling in the free state.

Co-crystallization and biochemical analyses with structurally defined oligosaccharides show the low reactivity of HS 3-OST-3 toward 6-O-sulfated substrates is due to inhibition of enzyme activity by 6-O-sulfated oligosaccharides.

Atomistic glycoprotein simulations reveal a site-specific availability of glycan substrates in time-resolved mass spectrometry of maturating enzyme kinetics.

NMR, ITC, and MD data show that the two domains of human galectin-8 independently recognize sialyl- and fucosyl-containing glycans.

Click handle-containing antigens can be used to study uptake, processing and presentation by immune cells.

Cathepsin B is an important protease within the lysosome, where it helps recycle proteins to maintain proteostasis.

This study provides a mechanistic description of how the membrane composition and lipid to protein ratio modulate amyloid kinetics of yeast prion protein.

Heterologous expression of an aromatic polyketide biosynthetic gene cluster recovered from a New Zealand soil metagenome library resulted in the discovery of new bioactive aureolic acids.

Evaluation of O(³P)-mediated cysteine oxidation in the proteome of a cell using dibenzothiophene-S-oxide derivatives as O(³P)-precursors.

A revision is proposed to the biosynthetic pathway to the well-known red pigment prodigiosin via a new thioester intermediate.

Sirtuin 2 (SIRT2) is a protein deacylase enzyme that removes acetyl groups and longer chain acyl groups from post-translationally modified lysine residues. Here, we developed small peptide-based inhibitors of its activity in living cells in culture.

Rad4/XPC DNA damage sensor protein specifically binds to a photocleavable NPOM-DNA adduct, and this recognition is abolished upon photo-cleavage of NPOM.

Using protein semi-synthesis, segmentally isotope-labelled variants of nucleosome-binding protein HMGN1 were generated with site-specific posttranslational modifications to explore their structural and functional effects.

Cyclic peptides containing unnatural amino acids can modulate Lys-48 ubiquitin chains in cells and animals.

Cyclodipeptide synthases recognize a minimalistic substrate to produce cyclic dipeptides in a tRNA-independent manner.

Programmed cell death 1 (PD-1) is an immune checkpoint regulating T-cell function. A catalytic antibody light chain, H34, could enzymatically degrade the PD-1 molecule. In addition, it inhibited the binding of PD-1 with PD-L1.

Using the protein–protein interaction of Mcl-1/Noxa, two methods for efficient modulator discovery are directly compared.

Macrolide fluorescent probes illuminate the interactions between antibiotics and bacteria, providing new insight into mechanisms of resistance.

A new helix-loop-helix peptide scaffold with dual ability to transport cargo across cancer cell membranes and disrupt mitochondrial membrane function.

We identified potent, functionalisable BMX inhibitors and revealed their covalent mode of binding to BMX by X-ray crystallography.

In-depth study of intriguing bacterial interrupted adenylation domains from seven distinct families and six different types.

Bifunctional peptides targeting both the translation and the replication machineries have been developed and shown to act as new antimicrobials.

Investigation of the downstream effects of NMT inhibition identified novel defense mechanism against chemical toxicity in fungal pathogen Z. tritici.

UDP-N-acetylglucosamine pyrophosphorylase (UAP1) catalyses the last step in eukaryotic biosynthesis of uridine diphosphate-N-acetylglucosamine (UDP-GlcNAc), converting UTP and GlcNAc-1P to the sugar nucleotide.