Site-specific traceless coupling of potent cytotoxic drugs to recombinant antibodies for pharmacodelivery

Aldehyde drugs are gaining increasing research interest, considering that aldehyde dehydrogenases overexpression is characteristic of cancer stem cells. Here, we describe the traceless site-specific coupling of a novel potent drug, containing an aldehyde moiety, to recombinant antibodies, which were engineered to display a cysteine residue at their N-terminus, or a 1,2-aminothiol at their C-terminus. The resulting chemically defined antibody-drug conjugates represent the first example in which a thiazolidine linkage is used for the targeted delivery and release of cytotoxic agents.     

Dynamic programming based algorithms for the discounted {0-1} knapsack problem

The discounted {0-1} knapsack problem (DKP) is an extension of the classical {0-1} knapsack problem (KP) that consists of selecting a set of item groups where each group includes three items and at most one of the three items can be selected. The DKP is more challenging than the KP because four choices of items in an item group diversify the selection of the items. Consequently, it is not possible to solve the DKP based on a classical definition of a core consisting of a small number of relevant variables. This paper partitions the DKP into several easier sub-problems to achieve problem reductions by imitating the core concept of the KP to derive an alternative core for the DKP. Numerical experiments with DP-based algorithms are conducted to evaluate the effectiveness of the problem partition by solving the partitioned problem and the original problem based on different types of DKP instances.     

Effects of structural modification on gene transfection and self-assembling properties of amphiphilic dendrimers

A library of novel amphiphilic, self-assembling dendrimers was designed and synthesised to evaluate the effects of structural changes on transfection efficiency.     

Efficient ribosomal peptidyl transfer critically relies on the presence of the ribose 2'-OH at A2451 of 23S rRNA

The ribosomal peptidyl transferase center is a ribozyme catalyzing peptide bond synthesis in all organisms. We applied a novel modified nucleoside interference approach to identify functional groups at 9 universally conserved active site residues. Owing to their immediate proximity to the chemical center, the 23S rRNA nucleosides A2451, U2506 and U2585 were of particular interest. Our study ruled out U2506 and U2585 as contributors of vital chemical groups for transpeptidation. In contrast the ribose 2'-OH of A2451 was identified as the prime ribosomal group with potential functional importance. This 2'-OH renders almost full catalytic power to the ribosome even when embedded into an active site of six neighboring 2'-deoxyribose nucleosides. These data highlight the unique functional role of the A2451 2'-OH for peptide bond synthesis among all other functional groups at the ribosomal peptidyl transferase active site.     

Estimates of Fourier Coefficients of Siegel Cusp Forms for Subgroups and in the Case of Small Weight

Here we develop estimates for Fourier coefficients of Siegelcusp forms. First we consider the case of Siegel modular formsfor the full modular group     

Phosphane Copper(I) Dicarboxylates: Synthesis and Their Potential Use as Precursors for the Spin‐coating Process in the Deposition of Copper

Dicopper dicarboxylates [(R₃P)_mCuXCu(PR₃)_m] ( 5a , X = O₂CCO₂, R = Ph, m = 2; 5b , X = O₂CCO₂, R = nBu, m = 3) were prepared by treatment of [Cu₂O] ( 1a ) with HO₂CCO₂H ( 2a ) in presence of PR₃ ( 4a , R = Ph; 4b , R = nBu). A further synthesis approach to mono‐ and dicopper dicarboxylates is given using an electrolysis cell equipped with Cu electrodes and charged with acids H₂X and phosphanes R₃P. Without addition of a base mononuclear [(nBu₃P)_mCuXH] ( 6a , m = 3, XH = O₂CCO₂H, 6b , m = 3, XH = O₂CCH₂CO₂H, 6c , m = 3, XH = O₂CCH₂CH₂CO₂H, 6d , m = 2, XH = O₂C‐2‐C₅H₄N‐6‐CO₂H) was formed, whereas in presence of NEt₃ ( 3 ), the dicopper systems [(R₃P)_mCuXCu(PR₃)_m] ( 5a , X = O₂CCO₂, R = Ph, m = 2; 5b , X = O₂CCO₂, R = nBu, m = 3; 5c , X = O₂CCH₂CO₂, R = nBu, m = 3; 5d , X = O₂CCH₂CH₂CO₂, R = nBu, m = 3; 5e , X = O₂C‐2‐C₅H₄N‐6‐CO₂, R = nBu, m = 3) were produced. When 6a reacted with [(tmeda)Zn(nBu)₂] ( 7 ), trimetallic [(tmeda)Zn((nBu₃P)₃CuO₂CCO₂)₂] ( 8 ) was accessible. In this heterobimetallic complex the Zn(tmeda) unit spans two CuO₂CCO₂ entities. The molecular structures of 5a , 6a and 6d in the solid state were determined by single X‐ray structure analysis. Complexes 5a and 6a are monomers, whereas 6d creates in the solid state a linear open chain coordination polymer by hydrogen bridge formation. Characteristic for 6d is the somewhat distorted trigonal bipyrimidal arrangement around the copper atom with the nBu₃P ligands in axial and the C₅H₃NCO₂H oxygen and nitrogen atoms in equatorial positions. In 5a the oxalate connectivity binds in a μ‐1,2,3,4 fashion being part of a planar Cu₂(oxalate) core. TG studies of several mono‐ and dicopper dicarboxylates were carried out. Release of the PR₃ ligands is recognized and the remaining Cu‐(di)carboxylate unit decomposes to afford elemental copper and CO₂. The deposition of copper onto pieces of PVD‐Cu oxidized silicon wafers by applying the spin‐coating process and using 5c and 5d as precursors is discussed.     

Spectroscopy vs. Electrochemistry: Catalyst Layer Thickness Effects on Operando/In Situ Measurements

In recent years, operando/in situ X-ray absorption spectroscopy (XAS) has become an important tool in the electrocatalysis community. However, the high catalyst loadings often required to acquire XA-spectra with a satisfactory signal-to-noise ratio frequently imply the use of thick catalyst layers (CLs) with large ion- and mass-transport limitations. To shed light on the impact of this variable on the spectro-electrochemical results, in this study we investigate Pd-hydride formation in carbon-supported Pd-nanoparticles (Pd/C) and an unsupported Pd-aerogel with similar Pd surface areas but drastically different morphologies and electrode packing densities. Our in situ XAS and rotating disk electrode (RDE) measurements with different loadings unveil that the CL-thickness largely determines the hydride formation trends inferred from spectro-electrochemical experiments, therewith calling for the minimization of the CL-thickness in such experiments and the use of complementary thin-film control measurements.     

Bulk and surface properties of blends with semifluorinated polymers and block copolymers

The goal of the investigation presented here is the development of extremely hydrophobic materials based on polysulfone that can be applied, for instance, as fouling-resistant membrane materials. The concept used is the addition of semifluorinated polymers to polysulfone in suitable blend compositions. The influence of molecular parameters like chain structure of the semifluorinated polymer (segmented block copolymers, random copolymers) and segment molecular weight on the state of phase separation in the bulk and its influence on the surface properties have been systematically examined. It could be shown that segmented block copolymers with semifluorinated polyester segments with intermediate segment molecular weight are more suitable in blends with polysulfone than random polysulfone copolymers having semifluorinated side chains with respect to form homogeneous thin films (coatings) with highly non-wetting properties.     

Thermolysis of Geminal Diazido Malonamides: Simple Access to Tetrazoles and Functionalization of In Situ Formed Isocyanates

In recent years, the development of synthetic methods to afford nitrogen-containing heterocycles has become increasingly popular. Among these, tetrazoles – an important class of aromatic heterocycles – are of significant interest for example, in medicinal chemistry serving as important bioisosteres. Herein, we present a method to easily access C-substituted tetrazoles via thermolysis of geminal diazido malonamides. Formation and functionalization of in situ formed isocyanates and corresponding reactions were also studied.     

Evaporation‐Driven Self‐Assembly of Colloidal Silica Dispersion: New Insights on Janus Particles

The evaporation driven self‐assembly of novel colloidal silica Janus particles was evaluated by scanning electron microscopy in comparison to unfunctionalized silica particles. The cyclodextrin‐ and azobenzene‐modified compound was obtained utilizing Pickering emulsion approach, in which the particles were immobilized on solidified wax droplets and subsequently functionalized. Silica particles were modified with 3‐aminopropyl trimethoxysilane and afterward reacted with tosyl‐β‐CD or phenylazo(benzoic acid), respectively. Mesoscopic structures of the colloidal dispersions, as dried films from aqueous solution, have been investigated by scanning electron microscopy and dynamic light scattering. Interestingly, it has been observed that the Janus particles show a significantly different evaporation‐induced assembly than the unmodified particles.