Towards Dynamic Drug Design: Identification and Optimization of β‐Galactosidase Inhibitors from a Dynamic Hemithioacetal System

A discovery strategy relying on the identification of fragments through resolution of a constitutional dynamic system, coupled to subsequent static ligand design and optimization, is demonstrated. The strategic design and synthesis of the best molecular fragments identified from a dynamic hemithioacetal system into static ligand structures yielded a range of β‐galactosidase inhibitors. Two series of structures mimicking the hemithioacetal motif were envisaged: thioglycosides and C‐glycosides. Inhibition studies provided important structural information for the two groups, and 1‐thiobenzyl‐β‐D ‐galactopyranoside demonstrated the best inhibitory effects.     

Glyconanomaterials: Synthesis,Characterization, and Ligand Presentation

Glyconanomaterials, nanomaterials carrying surface‐tethered carbohydrate ligands, have emerged and demonstrated increasing potential in biomedical imaging, therapeutics, and diagnostics. These materials combine the unique properties of nanometer‐scale objects with the ability to present multiple copies of carbohydrate ligands, greatly enhancing the weak affinity of individual ligands to their binding partners. Critical to the performance of glyconanomaterials is the proper display of carbohydrate ligands, taking into consideration of the coupling chemistry, the type and length of the spacer linkage, and the ligand density. This article provides an overview of the coupling chemistry for attaching carbohydrate ligands to nanomaterials, and discusses the need for thorough characterization of glyconanomaterials, especially quantitative analyses of the ligand density and binding affinities. Using glyconanoparticles synthesized by a versatile photocoupling chemistry, methods for determining the ligand density by colorimetry and the binding affinity with lectins by a fluorescence competition assay are determined. The results show that the multivalent presentation of carbohydrate ligands significantly enhances the binding affinity by several orders of magnitude in comparison to the free ligands in solution. The effect is sizeable even at low surface ligand density. The type and length of the spacer linkage also affect the binding affinity, with the longer linkage promoting the association of bound ligands with the corresponding lectins.     

Chemical composition of some forages and various residues from feeding value determinations

NDF, ADF, ‘cellulose’ and IVOMD residues, from feeding value determinations, were prepared from some forages, including straw, alkali-treated straw, grass and lucerne samples. The crude protein, cellulose, hemicellulose, uronic acid, Klason lignin, lignin and ash contents of these residues and the corresponding original forage samples were determined together with the relative composition of the neutral sugar constituents after acid hydrolysis. Cellulose, hemicellulose and Klason lignin were the main components in the NDF fractions but substantial amounts of crude protein (1–6%) also remained. Cellulose and Klason lignin were the main components in the ADF fractions, but 7–14% of the fractions was hemicellulose and 1–4% crude protein. Cellulose was the main component in the ‘cellulose’ fractions, but they also contained 8–13% hemicellulose, 2–7% Klason lignin and 2–11% ash. The composition of the IVOMD residues showed that cellulose and hemicellulose had been dissolved to about the same amounts (70–80%) and that most of the Klason lignin remained.     

Photo-click immobilization on quartz crystal microbalance sensors for selective carbohydrate-protein interaction analyses

A photoclick method based on azide photoligation and Cu-catalyzed azide-alkyne cycloaddition has been evaluated for the immobilization of carbohydrates to polymeric materials. The biomolecular recognition properties of the materials have been investigated with regard to applicable polymeric substrates and selectivity of protein binding. The method was used to functionalize a range of polymeric surfaces (polystyrene, polyacrylamide, poly(ethylene glycol), poly(2-ethyl-2-oxazoline), and polypropene) with various carbohydrate structures (based on α-D-mannose, β-D-galactose, and N-acetyl-β-D-glucosamine). The functionalized surfaces were evaluated in real-time studies of protein-carbohydrate interactions using a quartz crystal microbalance flow-through system with a series of different carbohydrate-binding proteins (lectins). The method proved to be robust and versatile, resulting in a range of efficient sensors showing high and predictable protein selectivities.     

Surface energy measurements from Griffith cracks in boron fibres

Journal of Materials Science -     

The initial stages of growth and the origin of proximate voids in boron fibres

The formation of so-called proximate voids (i.e. voids near the core-mantle interface) in boron fibres has been studied experimentally. The mantle growth was interrupted in very early stages of nucleation and growth of boron nodules on the tungsten wire substrate. Scanning electron microscope investigations of surface topography and cross-sections revealed a morphology of preferential nucleation of boron nodules along axial die-mark ridges on the tungsten wire surface, where tight parallel axial rows of growing nodules are formed which, particularly around deep wire surface grooves, may hedge in axially extended voids of a morphology earlier found to be typical of proximate voids. The physical conditions of this mechanism are studied with respect to geometry, surface energy and diffusion parameters.     

Self‐Assembly of Mechanoplasmonic Bacterial Cellulose–Metal Nanoparticle Composites

Nanocomposites of metal nanoparticles (NPs) and bacterial nanocellulose (BC) enable fabrication of soft and biocompatible materials for optical, catalytic, electronic, and biomedical applications. Current BC–NP nanocomposites are typically prepared by in situ synthesis of the NPs or electrostatic adsorption of surface functionalized NPs, which limits possibilities to control and tune NP size, shape, concentration, and surface chemistry and influences the properties and performance of the materials. Here a self‐assembly strategy is described for fabrication of complex and well‐defined BC–NP composites using colloidal gold and silver NPs of different sizes, shapes, and concentrations. The self‐assembly process results in nanocomposites with distinct biophysical and optical properties. In addition to antibacterial materials and materials with excellent senor performance, materials with unique mechanoplasmonic properties are developed. The homogenous incorporation of plasmonic gold NPs in the BC enables extensive modulation of the optical properties by mechanical stimuli. Compression gives rise to near‐field coupling between adsorbed NPs, resulting in tunable spectral variations and enhanced broadband absorption that amplify both nonlinear optical and thermoplasmonic effects and enables novel biosensing strategies.     

Gas temperature measurements using fibre Bragg grating during fire experiments in a tunnel

Gas temperature measurements with thermocouples are affected by radiation. This effect means that the temperature measured by a thermocouple can be far from the actual gas temperature. To study this effect and to compare the thermocouple readings with the readings of a fibre Bragg grating (FBG) sensor, fire experiments were performed in a model-scale tunnel. In this paper the results from two such fire experiments are presented. The temperatures measured using thermocouples with different diameters and the FBG sensor are compared and discussed. The “true” gas temperature, corrected for radiation effects from the thermocouples, was calculated from the results from the thermocouples with different diameters. The results show that the temperature measured by the FBG sensor is closer to the “true” gas temperature than is the case for any of the thermocouples used in these tests.