Themed collection Most popular 2021 chemical biology articles
Fluorescent probes for visualizing ROS-associated proteins in disease
Abnormal proteins, influenced by reactive oxygen species (ROS), are directly related to the development of various diseases.
Recent advances in activity-based probes (ABPs) and affinity-based probes (AfBPs) for profiling of enzymes
This review highlights the recent advances in the use of activity-based probes (ABPs) and affinity-based probes (AfBPs), and summarizes their design strategies (based on inhibitors and substrates) and detection approaches.
Synergizing the potential of bacterial genomics and metabolomics to find novel antibiotics
Antimicrobial resistance is a major public concern and novel antibiotics are largely based on natural products. We summarize recent analytical and genome based technological developments that gain increasing importance in the natural products field.
Improved broad-spectrum antibiotics against Gram-negative pathogens via darobactin biosynthetic pathway engineering
Heterologous expression of a synthetically engineered darobactin gene cluster in E. coli yields new darobactin derivatives with improved anti-Gram-negative activity. Targeted gene deletions provide first insights into biosynthetic steps.
Contributions to cytochrome c inner- and outer-sphere reorganization energy
Efficient delocalization of the redox-active molecular orbital (RAMO) in HtWT results in an increase in HAB value which in turn accelerates the electron transfer (ET) rate in spite of the higher reorganization energy (λ) than the HtQ64V mutant.
Coumarin luciferins and mutant luciferases for robust multi-component bioluminescence imaging
Near-infrared probes were developed from coumarin-modified luciferins and engineered luciferases, enabling facile multiplexed bioluminescence imaging.
RE-SELEX: restriction enzyme-based evolution of structure-switching aptamer biosensors
RE-SELEX is the first homogenous method for in vitro evolution of structure-switching DNA aptamers.
Mechanistic insights into dopaminergic and serotonergic neurotransmission – concerted interactions with helices 5 and 6 drive the functional outcome
Neurotransmitter contacts within the receptor binding site differentially contribute to the overall functional response: transmembrane helix (TM) 5 contacts promote G protein coupling whereas concerted TM5–TM6 contacts enhance β-arrestin recruitment.
Monitoring phagocytic uptake of amyloid β into glial cell lysosomes in real time
Glial cell phagocytosis of pH-dependent amyloid-β, AβpH, in live and fixed cultures, brain tissue sections, retina, cortex and in live animals useful for studying function in health and disease.
Discovering protein–protein interaction stabilisers by native mass spectrometry
Stabilising protein–protein interactions is challenging, yet therapeutically important. Native mass spectrometry can be used to monitor binding equilibria, allowing identification and measurement of novel protein–protein interaction stabilisers.
A copper-free and enzyme-free click chemistry-mediated single quantum dot nanosensor for accurate detection of microRNAs in cancer cells and tissues
A copper-free and enzyme-free click chemistry-mediated single quantum dot nanosensor enables sensitive detection of microRNAs in cancer cells and tissues.
Cellular delivery of dinucleotides by conjugation with small molecules: targeting translation initiation for anticancer applications
Ligand assisted cellular delivery of negatively charged dinucleotides, which are potential antagonists of the protooncogenic protein eIF4E.
Genetically-encoded discovery of proteolytically stable bicyclic inhibitors for morphogen NODAL
A two-fold symmetric linchpin (TSL) converts readily available phage-displayed disulfide peptide libraries to proteolytically stable bicyclic peptides. The bicyclic phage library was screened to discover an antagonist of NODAL morphogen.
Highly efficient on-DNA amide couplings promoted by micelle forming surfactants for the synthesis of DNA encoded libraries
Highly efficient forward and reverse on-DNA amide couplings were developed exploiting hydrophobic linkers in combination with the micelle forming surfactant TPGS-750M. The method is highly effective for a wide range of substrates in the synthesis of DNA-encoded libraries.
Cell–cell interactions via non-covalent click chemistry
We designed complementary artificial markers that were introduced on the surface of cells previously modified by metabolic glycoengineering. These recognition markers enable unnatural cell–cell adhesion through non-covalent click chemistry.
Rapid and robust cysteine bioconjugation with vinylheteroarenes
Vinylheteroarene linkers can chemoselectively modify cysteine residues in proteins and antibodies. These linkers give stable bioconjugates, and were used to synthesise efficacious antibody-drug conjugates.
Quantitative interrogation of protein co-aggregation using multi-color fluorogenic protein aggregation sensors
A little leak will sink a great ship! We prepared a series of multi-color protein aggregation sensors and developed a dual-color thermal shift assay to simultaneously and quantitatively report on protein co-aggregation of two different proteins.
Evaluation of fully-functionalized diazirine tags for chemical proteomic applications
The chemical proteomic properties of five diazirine-based, fully-functionalized photoaffinity tags, including a newly developed, minimal tag, were compared. This study provides guidance for the development of new photoaffinity probes.
Total synthesis, isolation, surfactant properties, and biological evaluation of ananatosides and related macrodilactone-containing rhamnolipids
We show that macrolactonization of gluco- and rhamnolipids dramatically interfere with their surfactant properties and biological activity.
Phase separation of p53 precedes aggregation and is affected by oncogenic mutations and ligands
Mutant p53 tends to form aggregates with amyloid properties, especially amyloid oligomers inside the nucleus, which are believed to cause oncogenic gain-of-function (GoF).
Linchpins empower promiscuous electrophiles to enable site-selective modification of histidine and aspartic acid in proteins
Linchpin-enabled promiscuous electrophile uncovers an unchartered reactivity landscape for the precision engineering of proteins.
Chemoproteomic profiling of itaconations in Salmonella
Bioorthogonal probes have been developed to enable quantitative and site-specific profiling of itaconate modifications in Salmonella.
Light-guided intrabodies for on-demand in situ target recognition in human cells
Nanobodies are ideal to visualize and modulate targets in living cells. We designed a versatile platform for generating photo-conditional intrabodies by genetic code expansion. After illumination, the intrabodies show fast and stable binding.
Rational design of iridium–porphyrin conjugates for novel synergistic photodynamic and photothermal therapy anticancer agents
Iridium–porphyrin conjugates assembled in nanoparticles are photosensitizers that exhibit excellent photothermal imaging and synergistic PDT and PTT in vivo.
Target-templated de novo design of macrocyclic D-/L-peptides: discovery of drug-like inhibitors of PD-1
In silico design of heterochiral cyclic peptides that bind to a specific surface patch on the target protein (PD-1, in this case) and disrupt protein–protein interactions.
Query-guided protein–protein interaction inhibitor discovery
Small-molecule protein–protein interaction inhibitors were prioritised on the basis of shape similarity to secondary structure-based queries incorporating hot-spot residues.
Nature-inspired dimerization as a strategy to modulate neuropeptide pharmacology exemplified with vasopressin and oxytocin
Structural and pharmacological study of parallel, antiparallel and N- to C-terminal cyclized homo- and heterodimers of vasopressin and oxytocin. This study spotlights dimerization as a strategy to modulate the pharmacology of neuropeptides.
Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes
Sulfonyl-triazole probes modified with a kinase recognition element are developed for live cell activity-based profiling to identify tyrosine sites located in catalytic and regulatory domains that are important for kinase function.
Traceless parallel peptide purification by a first-in-class reductively cleavable linker system featuring a safety-release
A first-in-class reductively cleavable linker system that enables parallel and traceless purification of peptides through a safety-release is introduced with three linker types and showcased by rapid production of 20 personalized neoantigen peptides.
Fluorogenic probes for detecting deacylase and demethylase activity towards post-translationally-modified lysine residues
We developed “turn-on” fluorescent probes that detect enzymatic lysine deacylation and demethylation critical for epigenetic and other cellular phenomena, using intramolecular O- to N-ester transfer reactions.
About this collection
This specially curated collection pulls together some of the most popular articles from 2021 in the field of chemical biology. The collection presents some outstanding contributions to the field, ranging from antibiotics to biosensors, and as with all Chemical Science articles – they are all completely free to access and read. We hope you enjoy browsing through this collection.