The past two decades have witnessed the emergence of macrocycles, including macrocyclic peptides, as a promising yet underexploited class of de novo drug candidates. Both rational/computational ...design and in vitro display systems have contributed tremendously to the development of cyclic peptide binders of either traditional targets such as cell-surface receptors and enzymes or challenging targets such as protein–protein interaction surfaces. mRNA display, a key platform technology for the discovery of cyclic peptide ligands, has become one of the leading strategies that can generate natural-product-like macrocyclic peptide binders with antibody-like affinities. On the basis of the original cell-free transcription/translation system, mRNA display is highly evolvable to realize its full potential by applying genetic reprogramming and chemical/enzymatic modifications. In addition, mRNA display also allows the follow-up hit-to-lead development using high-throughput focused affinity maturation. Finally, mRNA-displayed peptides can be readily engineered to create chemical conjugates based on known small molecules or biologics. This review covers the birth and growth of mRNA display and discusses the above features of mRNA display with success stories and future perspectives and is up to date as of August 2018.
Abstract
Engineering catalytic sites at the atomic level provides an opportunity to understand the catalyst’s active sites, which is vital to the development of improved catalysts. Here we show a ...reliable and tunable polyoxometalate template-based synthetic strategy to atomically engineer metal doping sites onto metallic 1T-MoS
2
, using Anderson-type polyoxometalates as precursors. Benefiting from engineering nickel and oxygen atoms, the optimized electrocatalyst shows great enhancement in the hydrogen evolution reaction with a positive onset potential of ~ 0 V and a low overpotential of −46 mV in alkaline electrolyte, comparable to platinum-based catalysts. First-principles calculations reveal co-doping nickel and oxygen into 1T-MoS
2
assists the process of water dissociation and hydrogen generation from their intermediate states. This research will expand on the ability to improve the activities of various catalysts by precisely engineering atomic activation sites to achieve significant electronic modulations and improve atomic utilization efficiencies.
Abstract
1T-MoS
2
and single-atom modified analogues represent a highly promising class of low-cost catalysts for hydrogen evolution reaction (HER). However, the role of single atoms, either as ...active species or promoters, remains vague despite its essentiality toward more efficient HER. In this work, we report the unambiguous identification of Ni single atom as key active sites in the basal plane of 1T-MoS
2
(Ni@1T-MoS
2
) that result in efficient HER performance. The intermediate structure of this Ni active site under catalytic conditions was captured by in situ X-ray absorption spectroscopy, where a reversible metallic Ni species (Ni
0
) is observed in alkaline conditions whereas Ni remains in its local structure under acidic conditions. These insights provide crucial mechanistic understanding of Ni@1T-MoS
2
HER electrocatalysts and suggest that the understanding gained from such in situ studies is necessary toward the development of highly efficient single-atom decorated 1T-MoS
2
electrocatalysts.
The efficient evolution of hydrogen through electrocatalysis is considered a promising approach to the production of clean hydrogen fuel. Platinum (Pt)‐based materials are regarded as the most active ...hydrogen evolution reaction (HER) catalysts. However, the low abundance and high cost of Pt hinders the large‐scale application of these catalysts. Active, inexpensive, and earth‐abundant electrocatalysts to replace Pt‐based materials would be highly beneficial to the production of cost‐effective hydrogen energy. Herein, a novel organoimido‐derivatized heteropolyoxometalate, Mo4‐CNP, is designed as a precursor for electrocatalysts of the HER. It is demonstrated that the carbon, nitrogen, and phosphorus sources derived from the Mo4‐CNP molecules lead to in situ confined carburization, phosphorization, and chemical doping on an atomic scale, thus forming nitrogen‐doped porous molybdenum carbide and phosphide hybrids, which exhibit remarkable electrocatalytic activity for the HER. Such an organically functionalized polyoxometalate‐assisted strategy described here provides a new perspective for the development of highly active non‐noble metal electrocatalysts for hydrogen evolution.
A novel organoimido‐derivatized heteropolyoxometalate, Mo4‐CNP, is designed as a precursor for hydrogen evolution reaction (HER) electrocatalysts. It is demonstrated that the carbon, nitrogen, and phosphorous sources derived from the Mo4‐CNP molecules lead to in situ and confined carburization, phosphorization, and chemical doping on the atomic scale, forming nitrogen‐doped porous molybdenum carbide and phosphide hybrids with remarkable electrocatalytic HER activity.
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Humans are exposed to an ever-increasing number of environmental toxicants, some of which have gradually been elucidated to be important risk factors for metabolic diseases, such as ...diabetes and obesity. These metabolism-sensitive diseases typically occur when key metabolic and signaling pathways were disrupted, which can be influenced by the exposure to contaminants such as endocrine disrupting chemicals (EDCs), along with genetic and lifestyle factors. This promotes the concept and research on environmental metabolism disrupting chemicals (MDCs). In addition, identifying endogenous biochemical markers of effect linked to disease states is becoming an important tool to screen the biological targets following environmental contaminant exposure, as well as to provide an overview of toxicity risk assessment. As such, the current review aims to contribute to the further understanding of exposome and human health and disease by characterizing environmental exposure and effect metabolic biomarkers. We summarized MDC-associated metabolic biomarkers in laboratory animal and human cohort studies using high throughput targeted and nontargeted metabolomics techniques. Contaminants including heavy metals and organohalogen compounds, especially EDCs, have been repetitively associated with metabolic disorders, whereas emerging contaminants such as perfluoroalkyl substances and microplastics have also been found to disrupt metabolism. In addition, we found major limitations in the effective identification of metabolic biomarkers especially in human studies, toxicological research on the mixed effect of environmental exposure has also been insufficient compared to the research on single chemicals. Thus, it is timely to call for research efforts dedicated to the study of combined effect and metabolic alterations for the better assessment of exposomic toxicology and health risks. Moreover, advanced computational and prediction tools, further validation of metabolic biomarkers, as well as systematic and integrative investigations are also needed in order to reliably identify novel biomarkers and elucidate toxicity mechanisms, and to further utilize exposome and metabolome profiling in public health and safety management.
Direct Hydroxylation of benzene to phenol with high yield and selectivity has been the goal of phenol industrial production. Photocatalysis can serve as a competitive method to realize the ...hydroxylation of benzene to phenol owing to its cost‐effective and environmental friendliness, however it is still a forbidding challenge to obtain good yield, high selectivity and high atom availability meanwhile. Here we show a series of supramolecular catalysts based on alkoxohexavanadate anions and quinolinium ions for the photocatalytic hydroxylation of benzene to phenol under UV irradiation. We demonstrate that polyoxoalkoxovanadates can serve as efficient catalysts which can not only stabilize quinolinium radicals but also reuse H2O2 produced by quinolinium ions under light irradiation to obtain excellent synergistic effect, including competitive good yield (50.1 %), high selectivity (>99 %) and high atom availability.
The readily available series green V supramolecular catalysts can catalyze the hydroxylation of benzene to phenol with high conversion, selectivity and atom efficiency.
Polyoxometalates (POMs)-porphyrin hybrids can serve as multifunctional materials with fascinating photocatalytic and photovoltaic properties. However, most previous POM-porphyrin hybrids are ...synthesized relied on electrostatic interactions to form ion pairs, which is not stable enough and subject to leaching and poor electronic communication. To our knowledge, no specific crystalline structure of direct covalently tris-functionalized POM-porphyrin hybrids has been identified. Herein, we discover an unprecedented polyoxometalates (POMs)-based photoresponsive cluster, {V6O13ZnC61H58N5O42}2– (denoted as V6–Zn-2Por), which can be synthesized by covalently grafting two tris-functionalized Zn-porphyrin ligands onto Lindqvist-type hexavanadate cluster using decavanadates (TBA)3H3V10O28 (denoted as V10, TBA = tetrabutylammonium cation) as precursor. Additionally, using tetraphenyl phosphonium as counterion, for the first time, a high-quality single crystal structure of the hybrid hexavanadate-porphyrin molecule is uncovered. Interestingly, the fluorescence emission spectra show that the fluorescence intensity of the organic–inorganic hybrid is partly quenched compared to pristine porphyrins, indicating possible energy/electron transfer between POMs cluster and porphyrin under light irradiation. Their UV–vis diffuse reflectance spectra show an extended absorption in the visible-light range. Finally, the as-prepared photoresponsive hexavanadate-porphyrin molecule is proved to exhibit effective photocatalytic activity toward removal of rhodamine B (an organic dye) under visible-light illumination.
Toda conformal field theories are natural generalizations of Liouville conformal field theory that enjoy an enhanced level of symmetry. In Toda conformal field theories this
higher-spin symmetry
can ...be made explicit, thanks to a path integral formulation of the model based on a Lie algebra structure. The purpose of the present document is to explain how this higher level of symmetry can manifest itself within the rigorous probabilistic framework introduced by R. Rhodes, V. Vargas and the first author in Cerclé (Probabilistic construction of simply-laced Toda conformal field theories, arXiv preprint,
arXiv:2102.11219
, 2021). One of its features is the existence of holomorphic currents that are introduced via a rigorous derivation of the Miura transformation. More precisely, we prove that the spin-three Ward identities, that encode higher-spin symmetry, hold in the
sl
3
Toda conformal field theory; as an original input we provide explicit expressions for the descendent fields which were left unidentified in the physics literature. This representation of the descendent fields provides a new systematic method to find the degenerate fields of the
sl
3
Toda (and Liouville) conformal field theory, which in turn implies that certain four-point correlation functions are solutions of a hypergeometric differential equation of the third order.
Here, we report a method for the one-pot ribosomal synthesis of macrocyclic depsipeptides. This method is based on a Ser-Pro-Cys-Gly (SPCG) motif discovered by in vitro selection of peptides for the ...function of self-acylation in the presence of a thioester acyl donor, which forms an O-acyl isopeptide bond via intramolecular S-to-O acyl transfer. Ribosomal synthesis of linear peptides containing the SPCG motif and a backbone “acyl donor” thioester at a downstream position results in spontaneous conversion to the corresponding cyclic depsipeptides (CDPs) in a nearly independent manner of ring size and sequence context. Mutational analysis of the SPCG motif revealed that the P and G residues are dispensable to some extent, but the arrangement of residues in SXCX is crucial for efficient acyl transfer, e.g., CPSG is much less efficient. Finally, one-pot ribosomal synthesis of macrocyclic depsipeptides with various ring sizes and sequences has been demonstrated. This synthetic method can facilitate the ribosomal construction of highly diverse CDP libraries for the discovery of de novo bioactive CDPs.
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