Dextramabs: A Novel Format of Antibody-Drug Conjugates Featuring a Multivalent Polysaccharide Scaffold

Antibody-drug conjugates (ADCs) are multicomponent biomolecules that have emerged as a powerful tool for targeted tumor therapy. Combining specific binding of an immunoglobulin with toxic properties of a payload, they however often suffer from poor hydrophilicity when loaded with a high amount of toxins. To address these issues simultaneously, we developed dextramabs, a novel class of hybrid antibody-drug conjugates. In these architectures, the therapeutic antibody trastuzumab is equipped with a multivalent dextran polysaccharide that enables efficient loading with a potent toxin in a controllable fashion. Our modular chemoenzymatic approach provides an access to synthetic dextramabs bearing monomethyl auristatin as releasable cytotoxic cargo. They possess high drug-to-antibody ratios, remarkable hydrophilicity, and high toxicity in vitro.     

A Highly Lewis Acidic Strontium ansa-Arene Complex for Lewis Acid Catalysis and Isobutylene Polymerization

The potential of a dicationic strontium ansa-arene complex for Lewis acid catalysis has been explored. The key to its synthesis was a simple salt metathesis from SrI₂ and 2 Ag[Al(OR^F)₄], giving the base-free strontium-perfluoroalkoxyaluminate Sr[Al(OR^F)₄]₂ (OR^F=OC(CF₃)₃). Addition of an ansa-arene yielded the highly Lewis acidic, dicationic strontium ansa-arene complex. In preliminary experiments, the complex was successfully applied as a catalyst in CO₂-reduction to CH₄ and a surprisingly controlled isobutylene polymerization reaction.     

Analysis of a Cahn–Hilliard–Brinkman model for tumour growth with chemotaxis

Phase field models recently gained a lot of interest in the context of tumour growth models. Typically Darcy-type flow models are coupled to Cahn–Hilliard equations. However, often Stokes or Brinkman flows are more appropriate flow models. We introduce and mathematically analyse a new Cahn–Hilliard–Brinkman model for tumour growth allowing for chemotaxis. Outflow boundary conditions are considered in order not to influence tumour growth by artificial boundary conditions. Existence of global-in-time weak solutions is shown in a very general setting.     

Aryl Triflates in On-Surface Chemistry

The reactivity of aryl triflates in on-surface C−C coupling is reported. It is shown that the triflate group in aryl triflates enables regioselective homo coupling with preceding or concomitant hydrodetriflation on Cu(111). Three different symmetrical π-systems with two and three triflate functionalities were used as monomers leading to oligomeric conjugated π-systems. The cascade, comprising different intermediates at different reaction temperatures as observed for one of the molecules, proceeds via initial removal of the trifluoromethyl sulfonyl group to give an aryloxy radical which in turn is deoxygenated to the corresponding aryl radical. Thermodynamically driven regioselective 1,2-hydrogen atom transfer leads to a translocated aryl radical which in turn undergoes coupling. For a sterically more hindered bistriflate, where one ortho position was blocked, dehydrogenative coupling occurred at remote position with good regioselectivity. Starting materials, intermediates as well as products were analyzed by scanning tunneling microscopy. Structures and suggested mechanism were further supported by DFT calculations.     

Regularized inversion of the Laplace transform for series of experiments

Not only in low-field nuclear magnetic resonance, Laplace inversion is a relevant and challenging topic. Considerable conceptual and technical progress has been made, especially for the inversion of data encoding two decay dimensions. Distortion of spectra by overfitting of even moderate noise is counteracted requiring a priori smooth spectra. In this contribution, we treat the case of simple and fast one-dimensional decay experiments that are repeated many times in a series in order to study the evolution of a sample or process. Incorporating the a priori knowledge that also in the series dimension evolution should be smooth, peak position can be stabilized and resolution improved in the decay dimension. It is explained how the standard one-dimensional regularized Laplace inversion can be extended quite simply in order to include regularization in the series dimension. Obvious improvements compared with series of one-dimensional inversions are presented for simulated as well as experimental data. For the latter, comparison with multiexponential fitting is performed.     

Ultrafast Single-Scan 2D NMR Spectroscopic Detection of a PHIP-Hyperpolarized Protease Inhibitor

Two-dimensional NMR spectroscopy is one of the most important spectroscopic tools for the investigation of biological macromolecules. However, due to the low sensitivity of NMR spectroscopy, it takes usually from several minutes to many hours to record such spectra. Here, the possibility of detecting a bioactive derivative of the sunflower trypsin inhibitor-1 (SFTI-1), a tetradecapeptide, by combining parahydrogen-induced polarization (PHIP) and ultrafast 2D NMR spectroscopy is shown. The PHIP activity of the inhibitor was achieved by labeling with O-propargyl-l -tyrosine. In 1D PHIP experiments a signal enhancement of a factor of approximately 1200 compared to standard NMR was found. This enhancement permits measurement of 2D NMR correlation spectra of low-concentrated SFTI-1 in less than 10 seconds, employing ultrafast single-scan 2D NMR detection. As experimental examples PHIP-assisted ultrafast single-scan TOCSY spectra of SFTI-1 are shown.     

Tailored side‐chain architecture of benzil voltage stabilizers for enhanced dielectric strength of cross‐linked polyethylene

The synthesis and physico‐chemical properties of seven benzil‐type voltage stabilizers are reported. The benzil core is substituted with alkyl chains of different length that are linked to the benzil core via an ester, ether, or tertiary amine group. All additives can be melt‐processed with low‐density polyethylene (LDPE). Fourier‐transform infrared spectroscopy confirms that benzil compounds are not affected by the LDPE cross‐linking reaction induced by dicumyl peroxide. Moreover, a combination of gel content measurements, thermal analysis, and small‐angle X‐ray scattering indicates that the presence of benzil voltage stabilizers does not significantly alter the microstructure of cross‐linked polyethylene (XLPE). Electrical tree inhibition experiments under high‐voltage alternating current conditions show that all investigated additives substantially enhance the dielectric strength of the insulating material at a concentration of only 10 mmol kg^?1. The highest improvement in dielectric strength, of more than 70% with respect to reference XLPE, is obtained with voltage stabilizers, which carry short (methyl) side chains that are linked to the benzil core via an ester or tertiary amine group. © 2014 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2014 , 52, 1047–1054     

Scarcity,competition, and value

We suggest a value for finite coalitional games with transferable utility that are enriched by non-negative weights for the players. In contrast to other weighted values, players stand for types of agents and weights are intended to represent the population sizes of these types. Therefore, weights do not only affect individual payoffs but also the joint payoff. Two principles guide the behavior of this value. Scarcity: the generation of worth is restricted by the scarcest type. Competition: only scarce types are rewarded. We find that the types’ payoffs for this value coincide with the payoffs assigned by the Mertens value to their type populations in an associated infinite game.