Bifunctional Molecules Research Articles

Low-temperature ALD/MLD growth of alucone and zincone thin films from non-pyrophoric precursors.

The combined atomic/molecular layer deposition (ALD/MLD) technique is emerging as a state-of-the-art synthesis route for new metal-organic thin-film materials with a multitude of properties by combining those of the inorganic and the organic material. A major part of the studies so far reported have focused on aluminum or zinc alkyls, so-called alucone and zincone films, typically grown from trimethyl aluminum (TMA) or diethyl zinc (DEZ) as the metal-bearing precursor, and a simple aliphatic bi-functional alcohol molecule such as ethylene glycol (EG) as the organic precursor. However, these common precursors possess certain disadvantages: both TMA and DEZ are pyrophoric, DEZ being additionally thermally unstable, while EG has a strong tendency for various unideal reaction modes. Here we report novel ALD/MLD processes for alucone and zincone films based on non-pyrophoric bis-diisopropylamido-[3-(N,N-dimethylamino)propyl] aluminum(III) [Al(NiPr2)2(DMP)] and bis-3-(N,N-dimethylamino)propyl zinc(II) [Zn(DMP)2] precursors in combination with hydroquinone (HQ) as the organic precursor. We demonstrate that the [Al(NiPr2)2(DMP)] + HQ and [Zn(DMP)2] + HQ ALD/MLD processes work even at record low deposition temperatures (140 °C and 60 °C, respectively) yielding high-quality and relatively stable Al-HQ and Zn-HQ thin films with appreciably high growth rates (2.8 Å / cycle and 3.2 Å / cycle, respectively). Moreover, these ALD/MLD processes are compatible with the corresponding ALD processes, i.e. [Al(NiPr2)2(DMP)] + H2O and [Zn(DMP)2] + H2O, for the Al2O3 and ZnO films, thus opening up new horizons for the fabrication of novel metal-oxide : organic superlattice structures for e.g. flexible gas-barrier coatings or wearable thermoelectrics.

Design and Exploration of Gut-Restricted Bifunctional Molecule with TGR5 Agonistic and DPP4 Inhibitory Effects for Treating Ulcerative Colitis

Design and Exploration of Gut-Restricted Bifunctional Molecule with TGR5 Agonistic and DPP4 Inhibitory Effects for Treating Ulcerative Colitis

PROTACs technology for treatment of Alzheimer's disease: Advances and perspectives.

Neurodegenerative diseases (NDs) are characteristic with progression of neuron degeneration, resulting in dysfunction of cognition and mobility. Many neurodegenerative diseases are because of proteinopathies that results from unusual protein accumulations and aggregations. The aggregation of misfolded proteins like β-amyloid, α-synuclein, tau, and polyglutamates are hallmarked in Alzheimer's disease (AD), which are undruggable targets, and usually do not respond to conventional small-molecule agents. Therefore, developing novel technology and strategy for reducing the levels of protein aggregates would be critical for treatment of AD. Recently, the emerging proteolysis targeting chimeras (PRPTACs) technology has been significantly considered for artificial and selective degradation of aberrant target proteins. These engineered bifunctional molecules engage target proteins to be degraded by either the cellular degradation machinery in the ubiquitin-proteasome system (UPS) or via the autophagy-lysosome degradation pathway. Although the application of PROTACs technology is preferable than oligonucleotide and antibodies for treatment of NDs, many limitations such as their pharmacokinetic properties, tissue distribution and cell permeabilities, still need to be corrected. Herein, we review the recent advances in PROTACs technology with their limitation for pharmaceutical targeting of aberrant proteins involved in Alzheimer's diseases. We also review therapeutic potential of dysregulated signaling such as PI3K/AKT/mTOR axis for the management of AD.

Influence of the Macromolecular architecture on the properties of biobased polyurethane tissue adhesives

Polyurethanes (PU) have recently emerged as promising biomaterials for tissue adhesive applications. Compared to other tissue adhesives, they offer substantial advantages such as the possibility to tailor adhesive strengths and curing times, for instance. All these properties are directly affected by the composition and final architecture. In this work, biobased two-components PU sealants were prepared, based on (i) an isocyanate-terminated prepolymer and (ii) a chain extender. Here, an exhaustive evaluation of the oligoester-diols and chain extenders influence on the sealants properties has been performed. In order to bring controlled variations on the final macromolecular architectures, three different prepolymers were prepared: two are based on poly(3-hydroxybutyrate) diol oligomers and another one on poly(lactic acid) diol oligomers, with a 50/50 isocyanate molar ratio of hexamethylene diisocyanate and biobased dimeryl diisocyanate. To study the chain extenders influence, five different aliphatic and linear bifunctional molecules were assessed, with varying length and functional groups reactivity. Ultimately, PUs obtained after the two-component systems curing were also fully characterized. They exhibited an overall good biocompatibility around 80%, with limited cytotoxicity. A wide range of physico-chemical and mechanical properties were also obtained, evidencing the importance of the macromolecular architecture on the systems final properties.

Characterization of GPVI- or GPVI-CD39-Coated Nanoparticles and Their Impact on In Vitro Thrombus Formation.

Traditional antithrombotic agents commonly share a therapy-limiting side effect, as they increase the overall systemic bleeding risk. A novel approach for targeted antithrombotic therapy is nanoparticles. In other therapeutic fields, nanoparticles have enabled site-specific delivery with low levels of toxicity and side effects. Here, we paired nanotechnology with an established dimeric glycoprotein VI-Fc (GPVI-Fc) and a GPVI-CD39 fusion protein, thereby combining site-specific delivery and new antithrombotic drugs. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles, NP-BSA, NP-GPVI and NP-GPVI-CD39 were characterized through electron microscopy, atomic force measurements and flow cytometry. Light transmission aggregometry enabled analysis of platelet aggregation. Thrombus formation was observed through flow chamber experiments. NP-GPVI and NP-GPVI-CD39 displayed a characteristic surface coating pattern. Fluorescence properties were identical amongst all samples. NP-GPVI and NP-GPVI-CD39 significantly impaired platelet aggregation. Thrombus formation was significantly impaired by NP-GPVI and was particularly impaired by NP-GPVI-CD39. The receptor-coated nanoparticles NP-GPVI and the bifunctional molecule NP-GPVI-CD39 demonstrated significant inhibition of in vitro thrombus formation. Consequently, the nanoparticle-mediated antithrombotic effect of GPVI-Fc, as well as GPVI-CD39, and an additive impact of CD39 was confirmed. In conclusion, NP-GPVI and NP-GPVI-CD39 may serve as a promising foundation for a novel therapeutic approach regarding targeted antithrombotic therapy.

Quantification of active selenols in cells: a selenol-specific recognition europium-switched signal-amplification ICP-MS approach.

Selenium (Se) is a mysterious thus tempting element playing a dual bio-chemical function, mainly through selenol, during life processes. Quantification of the selenols is thus of great significance for understanding the biological roles of Se, but remains a big challenge. Herein we report a selenol-specific recognition-mediated and europium (Eu) signal-switched amplification inductively coupled plasma mass spectrometry (ICP-MS) approach for quantifying the free active selenols (act-SeH) in cells. A bifunctional molecule, 2,4-dinitrobenzenesulfonyl-piperidin-4-yl-1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic europium (DNBS-DOTA-Eu), was designed and synthesized for the specific recognition and highly sensitive quantification of act-SeH via switching Se to more sensitive Eu ICP-MS signals. The limit of detection (LOD, 3σ) of 3.41 pg/mL (22.43 pmol/L), corresponding to the absolute mass LOD of 6.82 ag act-SeH per cell, is almost 25 times lower than 83.76 pg/mL (1.06 nmol/L), 167.52 ag, when monitoring 80Se. The results indicate that act-SeH in the selenite-precultured cancerous HepG2 and paracancerous HL7702 cells are 0.090 ± 0.002 pg/cell (n = 7) and 0.021 ± 0.006 pg/cell (n = 7), more than 4.28 times higher in HepG2 than in HL7702. Preliminary application of this approach to the cells from real hepatic tissue samples suggested that act-SeH has a positive relationship with the degree of hepatic disease. act-SeH in cells appears to be a very promising relevant index for understanding the biochemical functions of Se, besides the total Se in cells and blood serum and/or plasma.

De novo developed protein binders mimicking Interferon lambda signaling.

We hereby describe the process of design and selection of nonantibody protein binders mimicking cytokine signaling. We chose to mimic signaling of IFN-λ1, type 3 interferon (also known as IL-29) for its novelty and the importance of its biological functions. All four known interferons λ signal through binding to the extracellular domains of IL-28 receptor 1 (IL-28R1) and IL-10 receptor 2 (IL-10R2). Our binders were therefore trained to bind both receptors simultaneously. The bifunctional binder molecules were developed by yeast display, a method of directed evolution. The signaling capacity of the bivalent binders was tested by measuring phosphorylation of the JAK/STAT signaling pathway and production of mRNA of six selected genes naturally induced by IFN- λ1 in human cell lines. The newly developed bivalent binders offer opportunities to study cytokine-related biological functions and modulation of the cell behavior by receptor activation on the cell surfaces alternative to the use of natural IFN-λ.

One-pot synthesis of N-benzyl-2-aminobenzoic acid, via ring opening of isatoic anhydride derivative, and its antibacterial screening

2-(N-Benzyl) amino benzoic acid is a bifunctional molecule that could be produced from the reaction between isatoic anhydride and aryl halide. Analogues and derivatives of isatoic anhydride have wide application in pharmaceuticalsincluding antibacterial activity. The aim of this study is to synthesize, characterize and screen N-benzyl isatoic anhydride and 2-(N-benzyl) amino benzoic acid for antibacterial activity. The reaction of isatoic anhydride and benzyl bromide in the presence of potassium carbonate in DMSO at room temperature yielded N-benzyl isatoic anhydride, which under hydrolysis yielded 2-(N-benzyl) amino benzoic acid in which the anhydride ring is opened up. This compound was screened against Gram positive and negative bacteria. Moderate yield of 2-(N-benzyl) amino benzoic acid, a yellow crystal (melting point of 160-162oC, percentage yield 65 %, Rf 0.19) formed by ring opening of N-benzyl isatoic anhydride. The compound showed no antibacterial activity against Escherichia coli, Staphylococcus aureus, Pseudomonas pyocyanea, Salmonella typhimurium, Klebsiella aeruginosa and Bacillus subtilis. 2-(N-benzyl)amino benzoic was synthesized, characterized and showed no activity against bacteria.

High performance sky-blue perovskite light-emitting diodes enabled by a bifunctional phosphate molecule

Defects such as uncoordinated lead ions and surface charged defects are still one of critical issues for perovskite light-emitting diodes (PeLEDs). The presence of these defects can trap excitons, resulting in enhanced nonradiative recombination and thus poor efficiencies of PeLEDs. Defect passivation via passivation agents is an effective way to solve this issue. In this work, we introduce a bifunctional phosphate molecule 6,6′-(ethane-1,2-diyl)bis(dibenzo[c,e][1,2]oxaphosphinine 6-oxide) (DIDOPO) as a passivation agent into the perovskite, where DIDOPO can bind with the perovskite via the chemical interaction between the PO groups and uncoordinated Pb ions. Thus, the incorporation of DIDOPO effectively passivates the defects, leading to improved radiative recombination. Simultaneously, the as-prepared perovskite film produces dense and smooth morphology, which is favorable to good contact with the adjacent charge transport layers and the reduction of leakage current. As a result, the sky-blue PeLEDs modified by DIDOPO show improved efficiency with the maximum external quantum efficiency (EQEmax) of 5.52% and the average EQEmax of 5.09%. Furthermore, attributed to the alkyl chain as the bridge between the phosphate groups, DIDOPO accumulated at the perovskite surface is able to decrease hydrophilic behavior of the perovskite. The PeLEDs containing DIDOPO possess enhanced moisture resistance, remaining ca. 91–92% of the initial EQE after storage for 120 h in ambient atmosphere with the humidity of ca. 40%.

β-Alanine-Anchored SnO2 Inducing Facet Orientation for High-Efficiency Perovskite Solar Cells.

SnO2 films as a promising electron transport layer (ETL) have been widely used in planar-type perovskite solar cells to achieve an impressive improvement in the conversion efficiency. However, compared with a mesoporous ETL, the interfacial charge carrier transfer of the SnO2 ETL is severely limited due to the issues of oxygen vacancy defects and crystal lattice mismatch between SnO2 and the perovskite, which generally leads to the growth of randomly stacked and porous perovskite layers and subsequently impacts the charge transport and transfer properties. In this work, we developed a facile approach by inducing a bifunctional molecule, β-alanine, into the SnO2 ETL, which can serve as a bridge to modulate the interfacial charge transfer and the perovskite crystallization kinetics. Benefited by the interfacial β-alanine, we grew a highly orientational perovskite layer that exhibited superior charge transport properties. Meanwhile, the β-alanine caused an intimate connection between the perovskite and SnO2 to enhance the interfacial charge transfer. As a result, the power conversion efficiency (PCE) of the β-alanine-modified device achieved a much-improved value of 19.67% and showed high reproducibility. This work provides a way for developing a high-performance ETL toward the scalable fabrication of highly efficient PSCs.

An organic bifunctional redox active material for symmetric aqueous redox flow battery

Symmetric redox flow batteries utilizing a single redox active material as catholyte and anolyte, offer a plausible and unique strategy to alleviate cross-contamination issues during cycling, making them an ideal energy storage device for large scale applications. In this work, a low-cost riboflavin organic molecule is coupled with a 2,2,6,6-Tetramethylpiperidinyl-N-oxyl (TEMPO) radical molecule to form a single Riboflavin-TEMPO (RIBOTEMPO) bifunctional redox active material, which is used in both aqueous anolyte and catholyte. Cyclic voltammetry analysis of the combined molecule displays electrochemically reversible reactions for the redox couples at −0.72 V and 0.51 V versus Hg/Hg 2 SO 4 , leading to a theoretical cell voltage of 1.23 V. A symmetric cell testing demonstrated over 100 consecutive charge/discharge cycles with nearly 80% coulombic efficiency and capacity retention of 44.7% at a current density of 2.5 mA cm −2 . By utilizing a pH neutral supporting electrolyte, a low-cost, safe, and environmental-friendly redox flow battery is achieved. This work provides a pathway for the design and development of bifunctional redox active molecules for symmetric battery applications. • A bifunctional organic redox active material is designed and synthesized. • The battery displayed a high cell voltage of 1.23 V. • Molecule degradation is identified as the main cause of capacity loss.

Design and Antioxidant Properties of Bifunctional 2H-Imidazole-Derived Phenolic Compounds-A New Family of Effective Inhibitors for Oxidative Stress-Associated Destructive Processes.

The synthesis of inhibitors for oxidative stress-associated destructive processes based on 2H-imidazole-derived phenolic compounds affording the bifunctional 2H-imidazole-derived phenolic compounds in good-to-excellent yields was reported. In particular, a series of bifunctional organic molecules of the 5-aryl-2H-imidazole family of various architectures bearing both electron-donating and electron-withdrawing substituents in the aryl fragment along with the different arrangements of the hydroxy groups in the polyphenol moiety, namely derivatives of phloroglucinol, pyrogallol, hydroxyquinol, including previously unknown water-soluble molecules, were studied. The structural and antioxidant properties of these bifunctional 5-aryl-2H-imidazoles were comprehensively studied. The redox transformations of the synthesized compounds were carried out. The integrated approach based on single and mixed mechanisms of antioxidant action, namely the AOC, ARC, Folin, and DPPH assays, were applied to estimate antioxidant activities. The relationship “structure-antioxidant properties” was established for each of the antioxidant action mechanisms. The conjugation effect was shown to result in a decrease in the mobility of the hydrogen atom, thus complicating the process of electron transfer in nearly all cases. On the contrary, the conjugation in imidazolyl substituted phloroglucinols was found to enhance their activity through the hydrogen transfer mechanism. Imidazole-derived polyphenolic compounds bearing the most electron-withdrawing functionality, namely the nitro group, were established to possess the higher values for both antioxidant and antiradical capacities. It was demonstrated that in the case of phloroglucinol derivatives, the conjugation effect resulted in a significant increase in the antiradical capacity (ARC) for a whole family of the considered 2H-imidazole-derived phenolic compounds in comparison with the corresponding unsubstituted phenols. Particularly, conjugation of the polyphenolic subunit with 2,2-dimethyl-5-(4-nitrophenyl)-2H-imidazol-4-yl fragment was shown to increase ARC from 2.26 to 5.16 (104 mol-eq/L). This means that the considered family of compounds is capable of exhibiting an antioxidant activity via transferring a hydrogen atom, exceeding the activity of known natural polyphenolic compounds.

Grafting of organic molecular precursors onto ZrC(100)//t-ZrO2(001) surfaces: When experimental and theoretical studies meet

To control ZrC oxidation, one method is to coat the surface with SiC. This work therefore aims at grafting polymeric precursors on functionalized ZrC surfaces en-route to synthesizing ZrC/SiC core/shell composites. The exposed surface on the zirconia side of t-ZrO2(001) (tetragonal ZrO2) on top of a ZrC(100) substrate is first modified in presence of water. Water preferentially adsorbs molecularly and a subsequent functionalization with allylchlorodimethylsilane (ACDMS) in a SN reaction, appeared quite weak. However, the following grafting of a repetitive unit of the polymeric precursor, built from diphenylsilane and 1,4-diethynylbenzene monomers through a hydrosilylation reaction, is a highly favorable and exothermic reaction. As the main problem occurs during the nucleophilic substitution reaction between ACDMS and hydroxyl groups on the surface, two bifunctional organic molecules, but-3-enoic acid as well as glycolic acid, were also exploited. But-3-enoic acid adsorbed strongly to the Zr atoms of the surface, through chelating effects of the carboxylic acid group. The subsequent hydrosilylation reaction with a repetitive unit of the preceramic precursor was also a favorable exothermic reaction, indicating a promising approach for the grafting of organic macromolecules. In parallel, to associate experimental results, methyldiphenylsilane was grafted onto functionalized ZrC using but-3-enoic acid.

Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules.

Protein acetylation is a central event in orchestrating diverse cellular processes. However, current strategies to investigate protein acetylation in cells are often nonspecific or lack temporal and magnitude control. Here, we developed an acetylation tagging system, AceTAG, to induce acetylation of targeted proteins. The AceTAG system utilizes bifunctional molecules to direct the lysine acetyltransferase p300/CBP to proteins fused with the small protein tag FKBP12F36V, resulting in their induced acetylation. Using AceTAG, we induced targeted acetylation of a diverse array of proteins in cells, specifically histone H3.3, the NF-κB subunit p65/RelA, and the tumor suppressor p53. We demonstrate that targeted acetylation with the AceTAG system is rapid, selective, reversible and can be controlled in a dose-dependent fashion. AceTAG represents a useful strategy to modulate protein acetylation and should enable the exploration of targeted acetylation in basic biological and therapeutic contexts.

Surface Passivation with a Fluorocarbon-Based Pyridine Derivative for High-Crystallinity Perovskite Solar Cells with Efficiency Over 20% and Good Humidity Stability

Organic–inorganic hybrid perovskite solar cells (PSCs) are presently gaining significant attention owing to their high conversion efficiencies achieved in recent years. However, poor long-term stability against water and defects at film surfaces and grain boundaries are important factors causing performance degradation and rapid loss of the photovoltaic response. To remedy this, a pyridine derivative with long C–F chains (PFAD) is synthesized and employed as a passivator to reduce the trap states of perovskite and promote better humidity stability via antisolvent properties. The results demonstrate that the trap states of perovskite could be minimized by the presence of pyridinic nitrogen and then the formation of coordination bonds with undercoordinated Pb2+ ions. The resulting carrier recombination time is prolonged and verified via photoluminescence. The power conversion efficiency (PCE) of the PFAD-passivated perovskite solar cell increased to 20.48%, with practical elimination of hysteresis due to the high quality of the perovskite films. The significant gain generated via PFAD modification supports further applications in thin-film optoelectronic devices. Moreover, PFAD-modified devices exhibit enhanced humidity stability due to the protection of hydrophobic C–F chains from moisture; the PCE decreased about 15% after 30 days of exposure in a moisture ambient condition. Our work provides a promising strategy to further improve the performance and stability of perovskite solar cells by designing bifunctional organic molecules with passivation and hydrophobic effects.

Directed assembly of layered perovskite heterostructures as single crystals

The precise stacking of different two-dimensional (2D) structures such as graphene and MoS2 has reinvigorated the field of 2D materials, revealing exotic phenomena at their interfaces1,2. These unique interfaces are typically constructed using mechanical or deposition-based methods to build a heterostructure one monolayer at a time2,3. By contrast, self-assembly is a scalable technique, where complex materials can selectively form in solution4-6. Here we show a synthetic strategy for the self-assembly of layered perovskite-non-perovskite heterostructures into large single crystals in aqueous solution. Using bifunctional organic molecules as directing groups, we have isolated six layered heterostructures that form as an interleaving of perovskite slabs with a different inorganic lattice, previously unknown to crystallize with perovskites. In many cases, these intergrown lattices are 2D congeners of canonical inorganic structure types. To our knowledge, these compounds are the first layered perovskite heterostructures formed using organic templates and characterized by single-crystal X-ray diffraction. Notably, this interleaving of inorganic structures can markedly transform the band structure. Optical data and first principles calculations show that substantive coupling between perovskite and intergrowth layers leads to new electronic transitions distributed across both sublattices. Given the technological promise of halide perovskites4, this intuitive synthetic route sets a foundation for the directed synthesis of richly structured complex semiconductors that self-assemble in water.

Evidence of Supramolecular Origin of Selectivity in Solvent Extraction of Bifunctional Amidophosphonate Extractants with Different Configurations

ABSTRACT Extraction mechanisms of two bifunctional extractants which differ only by the grafting of an alkyl chain between their two functions were investigated at molecular and supramolecular scales to investigate the origin of their very different separation factors toward uranium and zirconium. Investigation of the complex structure with spectroscopic analysis (Fourier Transform Infra-Red (FTIR), ElectroSpray Ionization Mass Spectroscopy (ESI-MS) and Extended X-Ray Absorption Fine Structure (EXAFS)) demonstrated that alkylation does not affect the chelation mechanism of uranium and zirconium. Stoichiometries of complexes remain identical for both extractants: UO2L2(NO3)2 and zirconium polynuclear complexes are formed after extraction into the organic phase. The origin of selectivity was therefore investigated by considering the supramolecular self-assembly of the two bifunctional molecules. Small-Angle X ray and Neutrons Scattering (SAXS and SANS) showed that the highest separation factors between U and Zr are obtained when smaller aggregates are formed. The results of this study therefore suggests that the selectivity is controlled by the supramolecular self-assembly of the two extractant molecules. Thanks to a smaller packing parameter, the non-alkylated molecule forms bigger aggregates analogous to reverse micelles that can extract additional polar species in their polar core through a solubilization effect, thus decreasing the separation factor between uranium and zirconium.

Bifunctional small molecules that mediate the degradation of extracellular proteins

Targeted protein degradation (TPD) has emerged as a promising therapeutic strategy. Most TPD technologies use the ubiquitin-proteasome system, and are therefore limited to targeting intracellular proteins. To address this limitation, we developed a class of modular, bifunctional synthetic molecules called MoDE-As (molecular degraders of extracellular proteins through the asialoglycoprotein receptor (ASGPR)), which mediate the degradation of extracellular proteins. MoDE-A molecules mediate the formation of a ternary complex between a target protein and ASGPR on hepatocytes. The target protein is then endocytosed and degraded by lysosomal proteases. We demonstrated the modularity of the MoDE-A technology by synthesizing molecules that induce depletion of both antibody and proinflammatory cytokine proteins. These data show experimental evidence that nonproteinogenic, synthetic molecules can enable TPD of extracellular proteins in vitro and in vivo. We believe that TPD mediated by the MoDE-A technology will have widespread applications for disease treatment.

Destruction of DNA-Binding Proteins by Programmable Oligonucleotide PROTAC (O'PROTAC): Effective Targeting of LEF1 and ERG.

DNA‐binding proteins, including transcription factors (TFs), play essential roles in various cellular processes and pathogenesis of diseases, deeming to be potential therapeutic targets. However, these proteins are generally considered undruggable as they lack an enzymatic catalytic site or a ligand‐binding pocket. Proteolysis‐targeting chimera (PROTAC) technology has been developed by engineering a bifunctional molecule chimera to bring a protein of interest (POI) to the proximity of an E3 ubiquitin ligase, thus inducing the ubiquitination of POI and further degradation through the proteasome pathway. Here, the development of oligonucleotide‐based PROTAC (O'PROTACs), a class of noncanonical PROTACs in which a TF‐recognizing double‐stranded oligonucleotide is incorporated as a binding moiety of POI is reported. It is demonstrated that O'PROTACs of lymphoid enhancer‐binding factor 1 (LEF1) and ETS‐related gene (ERG), two highly cancer‐related transcription factors, successfully promote degradation of these proteins, impede their transcriptional activity, and inhibit cancer cell growth in vitro and in vivo. The programmable nature of O'PROTACs indicates that this approach is also applicable to destruct other TFs. O'PROTACs not only can serve as a research tool but also can be harnessed as a therapeutic arsenal to target DNA binding proteins for effective treatment of diseases such as cancer.

Effect of Substituents in Mussel-inspired Surface Primers on their Oxidation and Priming Efficiency.

Marine mussels contain an abundant catechol moiety, 3,4‐dihydroxyphenylalanine (DOPA), in their interfacial foot proteins. DOPA contributes to both surface adhesion and bridging between the surface and overhead proteins (surface priming) by taking advantage of the unique redox properties of catechol. Inspired by the mussel surface priming mechanism, herein we synthesized a series of DOPA‐mimetic analogs – a bifunctional group molecule, consisting of a catechol group and an acrylic group at the opposite ends. The surface primers with differently substituted (−COOH, −CH3) alkyl chains in the middle spacer were synthesized. Time‐dependent oxidation and redox potentials of the surface primers were studied in an oxidizing environment to gain a better understanding of the mussel‘s redox chemistry. The thickness and degree of priming of the surface primers on silicon‐based substrates were analyzed by ellipsometry and UV/Vis absorption spectroscopy. The post‐reactivity of the acrylic groups of the primed layer was first visualized through a reaction with an acrylic group‐reactive dye.