Evaluation of a two-stage screening procedure in the combinatorial search for serine protease-like activity

A series of peptidosteroid derivatives containing two independent peptide chains in which Ser and His are incorporated were synthesized by solid-phase peptide synthesis. The activity of the different compounds in the hydrolysis of the activated substrate NF31 was assessed in a stepwise fashion. First, the different resin-bound derivatives 6a-l and 6x-z were individually assayed for serine esterification in the absence of water. The use of a colored substrate allowed for a visual identification of the most active compounds. Through the inclusion of control substances, the involvement of histidine in the mechanism for serine acylation was shown. Second, the hydrolysis and methanolysis of the different acylated derivatives 8a-l and 8x were evaluated using UV spectroscopy, again indicating the involvement of histidine. The feasibility of applying the above procedures in a combinatorial context was proven via the screening of artificial libraries, created by mixing the different resin-bound peptidosteroid compounds. In this respect, the use of a photocleavable linker allowed for the unambiguous structural characterization of the selected members via application of single-bead electrospray tandem mass spectrometry.     

Multisensitive polymers based on 2‐vinylpyridine and N‐isopropylacrylamide *

Poly(2‐vinylpyridine) (P2VP) containing functionalized end groups was synthesized using nitroxyl‐mediated radical polymerization with a hydroxy‐functionalized stable free radical. It was shown that P2VP could be synthesized with variable molar masses and low polydispersities. The transformation of the hydroxy groups to an acrylic ester led to the formation of macromonomers. A free‐radical copolymerization of these macromonomers with N‐isopropylacrylamide gave a graft copolymer with a poly(N‐ispopropylacrylamide) backbone and P2VP side chains. Polymers containing different amounts of the monomers were synthesized. It was possible to vary both the amount of P2VP side chains at a constant chain length of the macromonomer and the chain length at a nearly constant chain number. The behavior of the multifunctional macromolecules at different temperatures and pH values was investigated using dynamic light scattering and DSC. The macromolecules were found to retain the specific properties of the homopolymers. The hydrodynamic radii of the synthesized graft copolymers were both dependent on the temperature and pH value. © 2001 John Wiley & Sons, Inc. J Polym Sci Part A: Polym Chem 39: 3797–3804, 2001     

Joint Distributions for Interacting Fluid Queues

Motivated by recent traffic control models in ATM systems, we analyse three closely related systems of fluid queues, each consisting of two consecutive reservoirs, in which the first reservoir is fed by a two-state (on and off) Markov source. The first system is an ordinary two-node fluid tandem queue. Hence the output of the first reservoir forms the input to the second one. The second system is dual to the first one, in the sense that the second reservoir accumulates fluid when the first reservoir is empty, and releases fluid otherwise. In these models both reservoirs have infinite capacities. The third model is similar to the second one, however the second reservoir is now finite. Furthermore, a feedback mechanism is active, such that the rates at which the first reservoir fills or depletes depend on the state (empty or nonempty) of the second reservoir.The models are analysed by means of Markov processes and regenerative processes in combination with truncation, level crossing and other techniques. The extensive calculations were facilitated by the use of computer algebra. This approach leads to closed-form solutions to the steady-state joint distribution of the content of the two reservoirs in each of the models.     

Synthesis of Block Copolymers Modified with Phosphonate Ester Groups Using Nitroxide‐Mediated Radical Polymerization

Summary: Phosphonate groups were introduced into block copolymers of styrene derivatives either as single end‐groups or as small blocks using nitroxide‐mediated radical polymerization. In order to combine the hydrophobic and hydrophilic segments, block copolymers with N,N‐dimethyl acrylamide were synthesized. After hydrolysis to phosphonic acid groups, adsorption of the polymer onto metal oxides was possible.

Conversion of the phosphonate groups by transesterification with trimethylbromosilane (TMBS), followed by hydrolysis of the silylester group.     

On the Modeling of Polyelectrolyte Gels

Summary: Ionic polymer gels are very attractive actuation materials with a great similarity to biological contractile tissues. They consist of a polymer network with bound charged groups and a liquid phase with mobile ions. Absorption and delivery of solvent lead to a considerably large change of volume. This swelling mechanism results from the equilibrium of different forces such as osmotic pressure forces, electrostatic forces and viscoelastic restoring forces and can be triggered by chemical (change of salt concentration or pH in the solution), thermal or electrical stimulation. In the present work, chemically and electrically stimulated electrolyte polymer gels in a solution bath are investigated. To describe the different phenomena occurring in these gels adequately, the modeling can be conducted on different scales. If only the global macroscopic behavior is of interest, the statistical theory which is capable to describe the global swelling ratio, is sufficient. By refining the scale, the mesoscopic coupled multi-field theory can be applied. Here, the chemical field is described by a convection-diffusion equation for the different mobile species. The electric field is directly obtained by solving the Poisson equation in the gel and solution domain. The mechanical field is formulated by the momentum equation. By further refining the scale, the whole structure can be investigated on the microscale by the discrete element (DE) method. In this model, the material is represented by distributed particles comprising a certain amount of mass; the particles interact with each other mechanically by a truss or beam network of massless elements. The mechanical behavior, i.e. the dynamics of the system, is followed by solving the Newton's equations of motion while the chemical field, i.e. the ion movement inside the gel and from the gel to the solution, is described by diffusion equations for the different mobile particles. All three formulations can give chemical, (electrical) and mechanical unknowns and all rely on the assumption that the concentration differences between the different regions of the gel and between gel and solution form the osmotic pressure difference, which is a main cause for the mechanical deformation of the polyelectrolyte gel film.     

Application of Polyelectrolytic Temperature-Responsive Hydrogels in Chemical Sensors

Summary: A rapidly expanding field of on-line process monitoring and on-line control in biotechnology, food industry, pharmaceutical industry, process chemistry, environmental measuring technology, water treatment and sewage processing requires the development of new micro fabricated reliable chemical and biosensors that are specific for particular species and can attain the analytic information in a faster, simpler and cheaper manner. Using a functionalised polymer coating in sensors provides the possibility to detect, transmit and record the information regarding the concentration change or the presence of a specific analyte (a chemical or biological substance that needs to be measured) by producing a signal proportional to the concentration of the target analyte. However, the sensor response time and signal reproducibility are limited by the visco-elastical and hysteresis behaviour of the polymer material. We propose some methods improving the properties of the chemical sensors on the basis of thermo-shrinking N-isopropylacrylamide (NIPAAm) copolymer gels.