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.     

Convergence of the Two‐Dimensional Dynamic Ising‐Kac Model to

The Ising‐Kac model is a variant of the ferromagnetic Ising model in which each spin variable interacts with all spins in a neighborhood of radius γ ^{? 1} for around its base point. We study the Glauber dynamics for this model on a discrete two‐dimensional torus for a system size and for an inverse temperature close to the critical value of the mean field model. We show that the suitably rescaled coarse‐grained spin field converges in distribution to the solution of a nonlinear stochastic partial differential equation. This equation is the dynamic version of the quantum field theory, which is formally given by a reaction‐diffusion equation driven by an additive space‐time white noise. It is well‐known that in two spatial dimensions such equations are distribution valued and a Wick renormalization has to be performed in order to define the nonlinear term. Formally, this renormalization corresponds to adding an infinite mass term to the equation. We show that this need for renormalization for the limiting equation is reflected in the discrete system by a shift of the critical temperature away from its mean field value.© 2016 by the authors. Communications on Pure and Applied Mathematics is published by Wiley Periodicals, Inc., on behalf of the Courant Institute of Mathematics.     

A new construction of the Clifford-Fourier kernel

In this paper, we develop a new method based on the Laplace transform to study the Clifford-Fourier transform. First, the kernel of the Clifford-Fourier transform in the Laplace domain is obtained. When the dimension is even, the inverse Laplace transform may be computed and we obtain the explicit expression for the kernel as a finite sum of Bessel functions. We equally obtain the plane wave decomposition and find new integral representations for the kernel in all dimensions. Finally we define and compute the formal generating function for the even dimensional kernels.     

Visible-Light-Induced Control over Reversible Single-Chain Nanoparticle Folding

We introduce a class of single-chain nanoparticles (SCNPs) that respond to visible light (λ_max=415 nm) with complete unfolding from their compact structure into linear chain analogues. The initial folding is achieved by a simple esterification reaction of the polymer backbone constituted of acrylic acid and polyethylene glycol carrying monomer units, introducing bimane moieties, which allow for the photochemical unfolding, reversing the ester-bond formation. The compaction and the light driven unfolding proceed cleanly and are readily followed by size exclusion chromatography (SEC) and diffusion ordered NMR spectroscopy (DOSY), monitoring the change in the hydrodynamic radius (R_H). Importantly, the folding reaction and the light-induced unfolding are reversible, supported by the high conversion of the photo cleavage. As the unfolding reaction occurs in aqueous systems, the system holds promise for controlling the unfolding of SCNPs in biological environments.     

Structures and Bioactivities of Steroidal Saponins Isolated from the Genera Dracaena and Sansevieria

The species Dracaena and Sansevieria, that are well-known for different uses in traditional medicines and as indoor ornamental plants with air purifying property, are rich sources of bioactive secondary metabolites. In fact, a wide variety of phytochemical constituents have been isolated so far from about seventeen species. This paper has reviewed the literature of about 180 steroidal saponins, isolated from Dracaena and Sansevieria species, as a basis for further studies. Saponins are among the most characteristic metabolites isolated from the two genera. They show a great variety in structural motifs and a wide range of biological activities, including anti-inflammatory, anti-microbial, anti-proliferative effects and, in most case, remarkable cytotoxic properties.     

Ultraviolet Absorption Induces Hydrogen‐Atom Transfer in G⋅C Watson–Crick DNA Base Pairs in Solution

Ultrafast deactivation pathways bestow photostability on nucleobases and hence preserve the structural integrity of DNA following absorption of ultraviolet (UV) radiation. One controversial recovery mechanism proposed to account for this photostability involves electron‐driven proton transfer (EDPT) in Watson–Crick base pairs. The first direct observation is reported of the EDPT process after UV excitation of individual guanine–cytosine (G?C) Watson–Crick base pairs by ultrafast time‐resolved UV/visible and mid‐infrared spectroscopy. The formation of an intermediate biradical species (G[?H]?C[+H]) with a lifetime of 2.9 ps was tracked. The majority of these biradicals return to the original G?C Watson–Crick pairs, but up to 10 % of the initially excited molecules instead form a stable photoproduct G*?C* that has undergone double hydrogen‐atom transfer. The observation of these sequential EDPT mechanisms across intermolecular hydrogen bonds confirms an important and long debated pathway for the deactivation of photoexcited base pairs, with possible implications for the UV photochemistry of DNA.