Peptide‐Coated Platinum Nanoparticles with Selective Toxicity against Liver Cancer Cells

Peptide‐stabilized platinum nanoparticles (PtNPs) were developed that have significantly greater toxicity against hepatic cancer cells (HepG2) than against other cancer cells and non‐cancerous liver cells. The peptide H‐Lys‐Pro‐Gly‐d Lys‐NH₂ was identified by a combinatorial screening and further optimized to enable the formation of water‐soluble, monodisperse PtNPs with average diameters of 2.5 nm that are stable for years. In comparison to cisplatin, the peptide‐coated PtNPs are not only more toxic against hepatic cancer cells but have a significantly higher tumor cell selectivity. Cell viability and uptake studies revealed that high cellular uptake and an oxidative environment are key for the selective cytotoxicity of the peptide‐coated PtNPs.     

Self‐Assembled Gold Arrays That Allow Rectification by Nanoscale Selectivity

The deposition of a monolayer nanoarray on the surface of a micrometer‐thick substrate is demonstrated, producing rectification characteristics at the nanoscale. The experimental results show that the heterogeneity of the structure and the charge density are the two key factors affecting rectification, which was confirmed with molecular dynamic (MD) and finite element simulations. Moreover, by altering the asymmetric electrolyte environment, the fabricated heterogeneous membrane can be used in energy conversion. This study provides insights into the mechanism underlying the generation of rectification and related factors, providing a theoretical basis for the characteristics of rectification.     

Full Selectivity Control in Cobalt(III)‐Catalyzed C−H Alkylations by Switching of the C−H Activation Mechanism

Selectivity control in hydroarylation‐based C−H alkylation has been dominated by steric interactions. A conceptually distinct strategy that exploits the programmed switch in the C−H activation mechanism by means of cobalt catalysis is presented, which sets the stage for convenient C−H alkylations with unactivated alkenes. Detailed mechanistic studies provide compelling evidence for a programmable switch in the C−H activation mechanism from a linear‐selective ligand‐to‐ligand hydrogen transfer to a branched‐selective base‐assisted internal electrophilic‐type substitution.     

An In‐tether Chiral Center Modulates the Helicity,Cell Permeability,and Target Binding Affinity of a Peptide

The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X‐ray diffraction analysis suggests that the absolute configuration of the in‐tether chiral center in helical form is R, which is in agreement with theoretical simulations. The relationship between the secondary structure of the short peptides and their biochemical/biophysical properties remains elusive, largely because of the lack of proper controls. The present strategy provides the only method for investigating the influence of solely conformational differences upon the biochemical/biophysical properties of peptides. The significant differences in permeability and target binding affinity between the peptide diastereomers demonstrate the importance of helical conformation.     

A Genetically Encoded,Phage‐Displayed Cyclic‐Peptide Library

Superior to linear peptides in biological activities, cyclic peptides are considered to have great potential as therapeutic agents. To identify cyclic‐peptide ligands for therapeutic targets, phage‐displayed peptide libraries in which cyclization is achieved by the covalent conjugation of cysteines have been widely used. To resolve drawbacks related to cysteine conjugation, we have invented a phage‐display technique in which its displayed peptides are cyclized through a proximity‐driven Michael addition reaction between a cysteine and an amber‐codon‐encoded N^?‐acryloyl‐lysine (AcrK). Using a randomized 6‐mer library in which peptides were cyclized at two ends through a cysteine–AcrK linker, we demonstrated the successful selection of potent ligands for TEV protease and HDAC8. All selected cyclic peptide ligands showed 4‐ to 6‐fold stronger affinity to their protein targets than their linear counterparts. We believe this approach will find broad applications in drug discovery.     

Targeting the Genome‐Stability Hub Ctf4 by Stapled‐Peptide Design

The exploitation of synthetic lethality by small‐molecule targeting of pathways that maintain genomic stability is an attractive chemotherapeutic approach. The Ctf4/AND‐1 protein hub, which links DNA replication, repair, and chromosome segregation, represents a novel target for the synthetic lethality approach. Herein, we report the design, optimization, and validation of double‐click stapled peptides encoding the Ctf4‐interacting peptide (CIP) of the replicative helicase subunit Sld5. By screening stapling positions in the Sld5 CIP, we identified an unorthodox i,i+6 stapled peptide with improved, submicromolar binding to Ctf4. The mode of interaction with Ctf4 was confirmed by a crystal structure of the stapled Sld5 peptide bound to Ctf4. The stapled Sld5 peptide was able to displace the Ctf4 partner DNA polymerase α from the replisome in yeast extracts. Our study provides proof‐of‐principle evidence for the development of small‐molecule inhibitors of the human CTF4 orthologue AND‐1.     

Isolable Silylene Ligands Can Boost Efficiencies and Selectivities in Metal‐Mediated Catalysis

A significant number of isolable silylenes are currently known. They have quickly developed from laboratory curiosities to useful ligands in metal‐mediated homogeneous catalysis. This includes their utilization in various catalytic transformations, such as C?C cross‐coupling, cyclotrimerization, hydroformylation, borylation, deuteration, hydrosilylation, amination, hydrogenation, and transfer semi‐hydrogenation reactions. Recent studies suggest that the silylene ligands surpass the steering properties of their phosphine and N‐heterocyclic carbene (NHC) analogues and provide excellent chemo‐, regio‐, and stereoselectivites. Mechanistic studies suggest that their promoted performance of metal‐mediated catalytic transformations results from a strong σ‐donor character along with cooperative effects of their Si^II centers. This Minireview covers the most recent advances in the field.     

Membrane Filtration with Liquids: A Global Approach with Prior Successes,New Developments and Unresolved Challenges

After 70 years, modern pressure‐driven polymer membrane processes with liquids are mature and accepted in many industries due to their good performance, ease of scale‐up, low energy consumption, modular compact construction, and low operating costs compared with thermal systems. Successful isothermal operation of synthetic membranes with liquids requires consideration of three critical aspects or “legs” in order of relevance: selectivity, capacity (i.e. permeation flow rate per unit area) and transport of mass and momentum comprising concentration polarization (CP) and fouling (F). Major challenges remain with respect to increasing selectivity and controlling mass transport in, to and away from membranes. Thus, prediction and control of membrane morphology and a deep understanding of the mechanism of dissolved and suspended solute transport near and in the membrane (i.e. diffusional and convective mass transport) is essential. Here, we focus on materials development to address the relatively poor selectivity of liquid membrane filtration with polymers and discuss the critical aspects of transport limitations. Machine learning could help optimize membrane structure design and transport conditions for improved membrane filtration performance.