Themed collection Most popular 2022 chemical biology articles

The molecular mechanisms of amyloid formation have been studied extensively in test tube reactions. This perspective article addresses the question to what extent these mechanisms apply to the complex situation in living cells and organisms.

IRED-catalyzed reductive aminations have progressed from mg to ton scale, through advances in enzyme discovery, protein engineering and process biocatalysis.

Triplex-forming oligonucleotides can target specific DNA sequences by binding in the duplex major groove. Chemical modifications and ligand binding have been explored, for use in a variety of biological applications.

The thermodynamics of amyloid formation has largely been neglected compared to kinetic studies. In this review, the current state of the experimental exploration of amyloid thermodynamics is presented and important open questions are highlighted.

Various prodrug conjugation strategies and innovative linker chemistries that exploit tumor-associated stimuli are summarized in this review to provide deep insights into the engineering of self-assembled prodrugs for efficient cancer therapy.

POC diagnostics are driven by the rapid advances in CRISPR, electrochemical and optical biosensors. Related emerging strategies are described and discussed from the perspective of facilitating the practical application of biosensors in POC testing.

Superoxo and hydroperoxo intermediates were cryotrapped at the copper active site of lytic polysaccharide monooxygenase using neutron protein crystallography.

The N-ter domain in HuPrP regulates the folding mechanism by tuning the long-range μs–ms dynamics. Removal of the N-ter domain triggers the formation of a stable β-enriched intermediate state inducing amyloid aggregates with HuPrP^Sc seeding activity.

A fluorescent immunosensor that lights up tumor biomarker p53 in living cells was developed based on the Q-body technology. The technology was further applied to the live cell monitoring of p53 levels, and live cell sorting based on p53 expression.

The reactivity, stereo-, and chemoselectivity of a tripeptide are so high that it catalyzes conjugate addition reactions with high stereoselectivity in complex compound mixtures—even in cell lysates.

Tetra-divinylpyrimidine (TetraDVP) linkers offer a method for the generation of antibody conjugates with modular cargo loading and excellent stability via all-in-one disulfide bridging.

Two enantiocomplementary myoglobin-based carbene transfer biocatalysts were developed for the synthesis of cyclopropylphosphonate esters with high diastereo- and enantioselectivity and in high yields.

In this article, we demonstrate the relatively unexplored potential of organic cages for use in targeted live cell imaging and highlight the importance of inter- and intramolecular interactions to stabilize and improve the performance of fluorophores.

We describe the development of covalent cyclic peptide ligands which target a chromatin methylation reader domain using a proximity-reactive sulfonyl fluoride moiety.

Modified catalytic antibodies targeting specific antigens are employed to investigate protein interactions and antigen interaction sites.

YnLac is an alkynyl-functionalized L-lactate analogue that is metabolically incorporated into L-lactylated proteins in live cells, enabling the fluorescence detection and proteomic identification of novel L-lactylated proteins.

A new strategy for selective tryptophan modification using triazolinedione (TAD) chemistry at pH 4 is shown on peptides and proteins. Additionally, off-target modification of tryptophan residues during the classical TAD-Y click reaction is uncovered.

Introducing unnatural base modifications site-specifically into the 3′-UTR of an mRNA bearing natural base modifications allows efficient visualization in cells by click chemistry. An enhanced protein expression in cells is observed from this twofold modified mRNA.

Efficient methodology to develop tumor-imaging fluorescent probes based on screening with our newly constructed probe library for aminopeptidase/protease (380 probes) and clinical samples has been established.

RaPID mRNA display was used for the discovery of antiviral cyclic peptides that potently and selectively inhibit SARS-CoV-2 M^pro. The most potent inhibitor exhibited a novel binding mode, interacting with residues across the homodimer interface.

Efficiency of targeted cell delivery of small molecules was enhanced in cells and animals via a novel well-defined bioconjugation platform combining site-specific antibody conjugation and XTEN polypeptides to enable high payload loading.

DNA-compatible direct oxidative coupling using various sulfur/selenium sources has been achieved, featuring pre-functionalization-free substrates and transition metal-free condition.

The pathology of Alzheimer's disease is connected to the aggregation of β-amyloid (Aβ) peptide, which in vivo exists as a number of length-variants. This study identifies the Aβ37/38/40 ratio that is maximally inhibitory to Aβ₄₂ aggregation.

Homodimerization of a proline-rich antimicrobial peptide via bioconjugation to perfluoroaromatic linkers confers increased antimicrobial, antibiofilm and immunomodulatory activity. The dimers are promising new therapeutic leads against WHO priority multidrug resistant bacteria.

HydroFlippers respond to membrane compression and hydration in the same fluorescence lifetime imaging microscopy histogram: the responses do not correlate.