Collision Characteristics between Ultracold Cesium <i>nP</i>Rydberg Atoms

We investigate the effect of van der Waals interactions and dipole-dipole interactions on collisional loss rate coefficients of Cs Rydberg nP states, and in detail analyze the variation of collisional loss coefficients under the initial Rydberg atomic velocity and van der Waals interactions. We obtain the total collisional loss coefficients for different nP states, and provide the possible ionization mechanism for the results of experimental observation using our analysis model.

PROTACs: great opportunities for academia and industry

Although many kinds of therapies are applied in the clinic,drug-resistance is a major and unavoidable problem.Another disturbing statistic is the limited number of drug targets,which are presently only 20–25%of all protein targets that are currently being studied.Moreover,the focus of current explorations of targets are their enzymatic functions,which ignores the functions from their scaffold moiety.As a promising and appealing technology,PROteolysis TArgeting Chimeras(PROTACs)have attracted great attention both from academia and industry for finding available approaches to solve the above problems.PROTACs regulate protein function by degrading target proteins instead of inhibiting them,providing more sensitivity to drug-resistant targets and a greater chance to affect the nonenzymatic functions.PROTACs have been proven to show better selectivity compared to classic inhibitors.PROTACs can be described as a chemical knockdown approach with rapidity and reversibility,which presents new and different biology compared to other gene editing tools by avoiding misinterpretations that arise from potential genetic compensation and/or spontaneous mutations.PRTOACs have been widely explored throughout the world and have outperformed not only in cancer diseases,but also in immune disorders,viral infections and neurodegenerative diseases.Although PROTACs present a very promising and powerful approach for crossing the hurdles of present drug discovery and tool development in biology,more efforts are needed to gain to get deeper insight into the efficacy and safety of PROTACs in the clinic.More target binders and more E3 ligases applicable for developing PROTACs are waiting for exploration.

FAK-targeting PROTAC as a chemical tool for the investigation of non-enzymatic FAK function in mice

Dear Editor,Animal models,most commonly mice,that lack a protein of interest play an important role in phenotypic and functional studies of a target gene,allowing researchers to answer various biological questions(Chaible et al,2010).At pre-sent,a variety of tools act at the DNA or RNA level to enable researchers to model gene function(and thus protein)deficiency,including nucleic acid based RNA interference(EI-bashir et al.,2001),antisense oligonucleotides(Schoch and Miller,2017),and genome editing-based CRISPR-Cas9(Doudna and Charpentier,2014)strategies.However,challenges remain.

Design,synthesis,and biological evaluation of multiple targeting antimalarials

Malaria still threatens global health seriously today.While the current discoveries of antimalarials are almost totally focused on single mode-of-action inhibitors,multi-targeting inhibitors are highly desired to overcome the increasingly serious drug resistance.Here,we performed a structure-based drug design on mitochondrial respiratory chain of Plasmodium falciparum and identified an extremely potent molecule,RYL-581,which binds to multiple protein binding sites of P.falciparum simultaneously(allosteric site of type Ⅱ NADH dehydrogenase,Q_(o) and Q_(i) sites of cytochrome bc_(1)).Antimalarials with such multiple targeting mechanism of action have never been reported before.RYL-581 kills various drug-resistant strains in vitro and shows good solubility as well as in vivo activity.This structurebased strategy for designing RYL-581 from starting compound may be helpful for other medicinal chemistry projects in the future,especially for drug discovery on membrane-associated targets.

Synthesis of Quaternary Carbon-Centered Benzoindolizidinones via Novel Photoredox-Catalyzed Alkene Aminoarylation: Facile Access to Tylophorine and Analogues

Photoredox-catalyzed aminoarylation and thioami-nation of unactivated alkenes have been developed,providing novel synthetic routes to access synthe-tically challenging quaternary carbon-centered benzoindolizidinones and trifluoromethylthiolated piperidines using readily available starting materials.Notably,these transformations were enabled by merging amidyl radical generation from N-alkyl benzamides with oxidant incorporation.Density functional theory calculations were performed to understand the reaction mechanism and to rationa-lize the regioselectivities.Moreover,the newly deve-loped catalytic aminoarylation provided a convenient synthetic route for natural product tylophorine and its gem-dimethyl analogues with greatly improved drug-like properties such as enhanced solubility and stability.