Overuse of conventional antibiotics as well as the slow pace of new antibiotic drug development leads to antimicrobial resistance (AMR). Because infections with multi‐drug resistant (MDR) pathogens have become a public health issue, the need for a novel class of antibiotics is urgent. Recently, antimicrobial peptides (AMPs) have emerged as a promising platform to fight against MDR bacteria ensuring broad‐spectrum antimicrobial activity and relatively low resistance emergence. Currently, a number of AMPs are undergoing clinical and preclinical trials against various infectious diseases. This review lists the 36 AMPs (27 clinical and 9 preclinical) with brief information about their origin, structure, mechanism, and development status. From the examples of AMPs under clinical investigation, we categorized several improvement strategies and highlighted directions for the future design of AMPs.

With the increasing interest and demand for epidermal electronics, a strong interface between a sensor and a biological surface is essential, yet achieving such interface is still a challenge. Here, a calcium (Ca)-modified biocompatible silk fibroin as a strong adhesive for epidermal electronics is proposed and the physical principles behind its interfacial and adhesive properties are reported. A strong adhesive characteristic (>800 N m −1 ) is observed because of the increase in both viscoelastic property and mechanical interlocking through the incorporation of Ca ions. Furthermore, additional key characteristics of the Ca-modified silk: reusability, stretchability, biocompatibility, and conductivity, are reported. These characteristics enable a wide range of applications as demonstrated in four epidermal electronic systems: capacitive touch sensor, resistive strain sensor, hydrogel-based drug delivery, and electrocardiogram monitoring sensor. As a reusable, biocompatible, conductive, and strong adhesive with water-degradability, the Ca-modified silk adhesive is a promising candidate for the next-generation adhesive for epidermal biomedical sensors.

The protist parasite Trypanosoma brucei is an obligate extracellular pathogen that retains its highly polarized morphology during cell division and has evolved a novel cytokinetic process independent of non-muscle myosin II. The polo-like kinase homolog TbPLK is essential for transmission of cell polarity during division and for cytokinesis. We previously identified a putative TbPLK substrate named Tip of the Extending FAZ 1 (TOEFAZ1) as an essential kinetoplastid-specific component of the T. brucei cytokinetic machinery. We performed a proximity-dependent biotinylation identification (BioID) screen using TOEFAZ1 as a means to identify additional proteins that are involved in cytokinesis. Using quantitative proteomic methods, we identified nearly 500 TOEFAZ1-proximal proteins and characterized 59 in further detail. Among the candidates, we identified an essential putative phosphatase that regulates the expression level and localization of both TOEFAZ1 and TbPLK, a previously uncharacterized protein that is necessary for the assembly of a new cell posterior, and a microtubule plus-end directed orphan kinesin that is required for completing cleavage furrow ingression. The identification of these proteins provides new insight into T. brucei cytokinesis and establishes TOEFAZ1 as a key component of this essential and uniquely configured process in kinetoplastids.

Electrocatalytic conversion of CO2 into value-added products offers a new paradigm for a sustainable carbon economy. For active CO2 electrolysis, the single-atom Ni catalyst has been proposed as promising from experiments, but an idealized Ni–N4 site shows an unfavorable energetics from theory, leading to many debates on the chemical nature responsible for high activity. To resolve this conundrum, here we investigated CO2 electrolysis of Ni sites with well-defined coordination, tetraphenylporphyrin (N4–TPP) and 21-oxatetraphenylporphyrin (N3O–TPP). Advanced spectroscopic and computational studies revealed that the broken ligand-field symmetry is the key for active CO2 electrolysis, which subordinates an increase in the Ni redox potential yielding NiI. Along with their importance in activity, ligand-field symmetry and strength are directly related to the stability of the Ni center. This suggests the next quest for an activity–stability map in the domain of ligand-field strength, toward a rational ligand-field engineering of single-atom Ni catalysts for efficient CO2 electrolysis.

Cationic, amphipathic host defense peptides represent a promising group of agents to be developed for anticancer applications. Poly-N-substituted glycines, or peptoids, are a class of biostable, peptidomimetic scaffold that can display a great diversity of side chains in highly tunable sequences via facile solid-phase synthesis. Herein, we present a library of anti-proliferative peptoids that mimics the cationic, amphipathic structural feature of the host defense peptides and explore the relationships between the structure, anticancer activity and selectivity of these peptoids. Several peptoids are found to be potent against a broad range of cancer cell lines at low-micromolar concentrations including cancer cells with multidrug resistance (MDR), causing cytotoxicity in a concentration-dependent manner. They can penetrate into cells, but their cytotoxicity primarily involves plasma membrane perturbations. Furthermore, peptoid 1, the most potent peptoid synthesized, significantly inhibited tumor growth in a human breast cancer xenotransplantation model without any noticeable acute adverse effects in mice. Taken together, our work provided important structural information for designing host defense peptides or their mimics for anticancer applications. Several cationic, amphipathic peptoids are very attractive for further development due to their high solubility, stability against protease degradation, their broad, potent cytotoxicity against cancer cells and their ability to overcome multidrug resistance.

Peptoids are a rapidly developing class of biomimetic polymers based on oligo-N-substituted glycine backbones, designed to mimic peptides and proteins. Inspired by natural antimicrobial peptides, a group of cationic amphipathic peptoids has been successfully discovered with a potent and broad-spectrum activity against pathogenic bacteria; however, there are limited studies to address the in vivo pharmacokinetics of the peptoids. Herein, 64Cu labeled DOTA conjugates of three different peptoids and two control peptides were synthesized and assayed in vivo by both biodistribution studies and small animal positron emission tomography (PET). The study was designed in a way to assess how structural differences of the peptidomimetics affect in vivo pharmacokinetics. As amphipathic molecules, major uptake of the peptoids occurred at the liver. Increased kidney uptake was observed by deleting one hydrophobic residue in the peptoid, and 64Cu-3 achieved the highest kidney uptake of all the conjugates tested in this study. In comparison to peptides, our data indicated that peptoids had general in vivo properties of higher tissue accumulation, slower elimination, and higher in vivo stability. Different administration routes (intravenous, intraperitoneal, and oral) were investigated with peptoids. When administered orally, the peptoids showed poor bioavailability, reminiscent to that of peptide. But, remarkably longer passage through the gastrointestinal (GI) tract without rapid digestion was observed for peptoids. These unique in vivo properties of peptoids were rationalized by efficient cellular membrane permeability and protease resistance of peptoids. The results observed in the biodistribution studies could be confirmed by the PET imaging, which provides a reliable way to evaluate in vivo pharmacokinetic properties of peptoids noninvasively and in real time. The pharmacokinetic data presented here can provide an insight for further development of the antimicrobial peptoids as pharmaceuticals.

in enediolate intermediates. [1] Recently, a similar mechanism of CO 2 insertion at the unsaturated carbon bond has been adopted in the synthesis of carboxylic acids employing alkynes, [2] α-olefins [3] and internal alkenes as substrates. [4] These methods enabled CO 2 to be harnessed as a renewable one-carbon building block; however, the valorization of CO 2 is still challenging because the gas is thermodynamically and kinetically stable. [5] Consequently, numerous advances in chemical carboxylation using CO 2 have relied on highly reactive organometallic nucleophiles to facilitate the reaction. [5,6] Recent reports have demonstrated that the elaborate design of organometallic nucleophiles is the primary requisite for modulation of site-selectivity and extension of substrates in carboxylation. [6,7] Recently, Martin and co-workers developed an elegant protocol for site-selectivity tunable carboxylation via nickel hydride or nickelalactone formation for the extensive scope of unsaturated hydrocarbons, such as styrenes, alkenes and alkynes. [8] As an alternative approach, heterogeneously catalyzed electrochemical carboxylation has gained increasing attention. This reactions are mainly driven by reductive electrical potential on a cathode electrode. [9] Therefore, the reduction reaction takes place in the absence of a reducing agent and the reducing power can be easily controlled by the applied potentials. Among the unsaturated hydrocarbon feedstocks, this study focused on the electrochemical carboxylation of styrene as a representative model.In the carboxylation of styrene using CO 2 , hydrocarboxylation of the αor β-position and dicarboxylation at both positions are feasible. Vianello and co-workers first pioneered the electrochemical dicarboxylation of styrene to form 2-phenylsuccinic acid (1). [10] Since then, several succeeding works on the electrochemical carboxylation of styrene have reported dicarboxylation as a primary reaction both in the presence [11] and absence [12] of homogeneous catalysts. These studies proposed the electrochemical formation of β-carboxylate radical anions as a key intermediate, followed by additional CO 2 insertion to the benzylic position. [12a,c] It has been hypothesized that the electrochemical carboxylation of styrene is mostly carried out by the dicarboxylation pathway, whereas addition of water as protic agent can change reaction pathway to The carboxylation of hydrocarbons using CO 2 as a one-carbon building block is an attractive route for the synthesis of carboxylic acids and their derivatives. Until now, chemical carboxylation catalyzed by organometallic nucleophiles and reductants has been generally adopted particularly for the precise selectivity control of carboxylation sites. As another approach, electrochemical carboxylation has been attempted but these carboxylation reactions are limited to only a few pathways. In the case of styrene, dicarboxylation at the αand β-positions is mostly observed with electrochemical carboxylation while site-selective hydrocarboxy...

The degree of peptoid helicity can be effectively modulated by position-specific incorporation of α-chiral aromatic monomers. In this study, we report the structural role of each monomer position collected from 30 comprehensive model peptoid oligomers demonstrating a meticulous manner to fine-tune peptoid secondary structures.