Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain
the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in
Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles
and JavaScript.
Discovering ligands that modulate the function of biomolecules can be achieved by using DNA-encoded libraries that link the function of a synthetic molecule to an amplifiable nucleic acid tag. Such technologies do not make full use of the principles of Darwinian selection, but now a team led by Nicolas Winssinger has developed a strategy to assemble libraries of macrocyclic-like structures (Dsuprabodies) that undergo iterative cycles of selection, amplification and diversification. The method was validated with selections against streptavidin and used to discover a potent and selective binder for the protein PD-L1. The cover image shows an artistic representation of a suprabody interacting with PD-L1.
Chemistry plays a key role in tackling today’s challenges and ensuring a sustainable future. Since 2019, IUPAC has been identifying technologies with the potential to advance our society and improve our quality of life.
Lara Mosunmola Lalemi, PhD student at the University of Bristol and founder of the Creative Tuition Collective, shares with Nature Chemistry some of her projects — from climate chemistry to social justice — to improve our environment in all senses of the term.
Aryl aminooxetanes are used as amide bioisosteres in drug discovery but there are limited strategies for synthesizing them. Now, an approach has been developed that simplifies the synthesis of these privileged motifs, enabling a broad range of amines to be used.
Despite the disordered and dynamic environment in which it occurs, photosynthetic light harvesting is highly efficient. Now, measurements of energy transfer in single photosynthetic antennae show how these structures deal with protein fluctuations, robustly transferring the energy before it is lost.
The emergence of protometabolic reactions that evolved into today’s metabolic pathways is unclear. Now, evidence suggests that the chemical origin of biological carbon metabolism may have relied on the versatility of a single primitive C1 feedstock molecule — hydrogen cyanide.
The adsorption of molecules onto a surface from solution generally proceeds spontaneously by means of an equilibrium process. Now, it has been shown that macrocycles can be pumped onto a MOF substrate through the formation of mechanical bonds in a ratcheting mechanism that results in an out-of-equilibrium state.
DNA-encoded libraries can be applied in a diverse range of applications beyond simple binding assays. This Perspective covers the recent progress in using DNA-encoded chemical libraries to investigate complex biological targets and discusses their potential to identify structures that elicit function or possess other useful properties.
DNA-encoded libraries facilitate the discovery of ligands that interact with biomolecules but such technologies do not take full advantage of the principles of Darwinian selection. Now, libraries of conformationally constrained peptides (Dsuprabodies) have been assembled using a strategy that allows for iterative cycles of selection, amplification and diversification. This method was validated with selections against streptavidin and PD-L1.
In photosynthesis, photoenergy transfers through chromophore-containing proteins, which exhibit thermal fluctuations that change the positions of the chromophores. Now the ultrafast dynamics in allophycocyanin—a cyanobacterial light-harvesting protein—have been measured using single-molecule pump–probe spectroscopy. The data show that energy transfer precedes protein-induced photophysical heterogeneity, ensuring that light harvesting is robust to the heterogeneity.
Sulfonyl fluorides typically react with nucleophiles exclusively at sulfur, leading to the substitution of fluoride, as is the case in SuFEx reactions. Now, an alternative defluorosulfonylative reaction has been developed, coupling 3-aryloxetane sulfonyl fluorides with amines to generate amino-oxetanes. The mild conditions and high functional group tolerance enable the preparation of oxetane analogues of benzamide drugs via oxetane carbocation intermediates.
It’s unclear how protometabolic reactions emerged and evolved into extant metabolic pathways such as the tricarboxylic acid cycle. Now, it has been shown that cyanide acts as a mild and efficient reducing agent, mediating abiotic transformations of tricarboxylic acid intermediates and derivatives.
The synthesis of chiral interlocked molecules in which the mechanical bond provides the only source of stereochemistry remains challenging. Now, a chiral interlocked auxiliary approach to mechanically planar chiral rotaxanes has been developed and its potential demonstrated through the synthesis of a range of difficult targets with high enantioselectivity.
Without directing auxiliaries, the addition of carbogenic groups to unactivated alkenes is typically inefficient and suffers from poor regioselectivity. Now, a directing-group-free, nickel catalyst-controlled strategy has been developed, enabling the site-selective dicarbofunctionalization of a broad array of activated and unactivated alkenes.
The complex link between protein sequence and phase behaviour for a family of prion-like low-complexity domains (PLCDs) has now been revealed. The results have uncovered a set of rules—which are interpreted using a stickers-and-spacers model—that govern the sequence-encoded phase behaviour of such PLCDs and enable physicochemical rationalizations that are connected to the underlying sequence composition.
Water-walking insects harness capillary forces by changing body posture to climb or descend the meniscus between water and a solid object. Now, autonomous aqueous-based synthetic systems have been shown to overcome the meniscus barrier and shuttle cargo subsurface between a landing site and targeted drop-off sites.
A photoredox-mediated SNAr reaction has now been developed for the direct radiofluorination of unactivated aryl halides. A series of arenes can be radiofluorinated in a site-selective manner from readily available aryl halide precursors under mild conditions. This strategy allows efficient 19F/18F isotopic exchange, enabling rapid PET probe diversification and clinical tracer preparation.
Histone H1 binds to nucleosomes with ultrahigh affinity, implying residence times incompatible with efficient biological regulation. Now it has been shown that the disordered regions of H1 retain their large-amplitude dynamics on the nucleosome, which enables a charged disordered histone chaperone to invade the H1–nucleosome complex and vastly accelerate H1 dissociation.
Aromatic systems that interact non-covalently are important in many settings, such as base-pair stacking and DNA–drug interactions; however, their excited-state molecular dynamics are not fully understood. Now, intermolecular Coulombic decay in benzene dimers has been observed. The process is initiated by electron-impact ionization and proceeds through ultrafast energy transfer between the benzene molecules.
Amina Schartup relates how our understanding of methylmercury has changed in the 170 years since it was discovered — as well as some of the disasters that occurred along the way.