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Biomedical subjects

Jeffrey T Koberstein

Publications and source records attributed to Jeffrey T Koberstein.

7 recordsLinked to original sources

Photogenerated glycan arrays identify immunogenic sugar moieties of Bacillus anthracis exosporium.

Using photogenerated glycan arrays, we characterized a large panel of synthetic carbohydrates for their antigenic reactivities with pathogen-specific antibodies. We discovered that rabbit IgG antibodies elicited by Bacillus anthracis spores specifically recognize a tetrasaccharide chain that decorates the outermost surfaces of the B. anthracis exosporium. Since this sugar moiety is highly specific for the spores of B. anthracis, it appears to be a key biomarker for detection of B. anthracis spores and development of novel vaccines that target anthrax spores.

Animals↗

Toward the syntheses of universal ligands for metal oxide surfaces: controlling surface functionality through click chemistry.

A new means for functionalizing metal oxide surfaces, specifically nanoparticles, is demostrated. This process involves the design of stable ligands that bind strongly to the surface of metal oxides and can undergo further chemical modification via click chemistry, with both small molecules as well as polymers, to yield metal oxide surfaces with tailored functionality. The nanoparticles are stable and easily dispersed in both polar and nonpolar solvents, a property that is controlled by the ligand. The resultant nanoparticles were characterized by TEM, TGA, FTIR, and NMR.

Journal Article↗

Photoactive additives for cross-linking polymer films: Inhibition of dewetting in thin polymer films.

In this report, we describe a versatile photochemical method for cross-linking polymer films and demonstrate that this method can be used to inhibit thin polymer films from dewetting. A bifunctional photoactive molecule featuring two benzophenone chromophores capable of abstracting hydrogen atoms from various donors, including C-H groups, is mixed into PS films. Upon exposure to UV light, the bis-benzophenone molecule cross-links the chains presumably by hydrogen abstraction followed by radical recombination. Photoinduced cross-linking is characterized by infrared spectroscopy and gel permeation chromatography. Optical and atomic force microscopy images show that photocrosslinked polystyrene (PS) thin films resist dewetting when heated above the glass transition temperature or exposed to solvent vapor. PS films are inhibited from dewetting on both solid and liquid substrates. The effectiveness of the method to inhibit dewetting is studied as a function of the ratio of cross-linker to macromolecule, duration of exposure to UV light, film thickness, the driving force for dewetting, and the thermodynamic nature of the substrate.

Cross-Linking Reagents↗

Synthesis of degradable model networks via ATRP and click chemistry.

A simple scheme involving atom transfer radical polymerization (ATRP) from a bifunctional initiator, conversion of the bromine end groups of the resulting telechelic polymer to azides, and cross-linking of this azido-telechelic macromonomer with multi-acetylene functionalized small molecules via copper-catalyzed azide-alkyne cycloaddition was employed to prepare the first tert-butyl acrylate model networks. This general scheme is wide in scope, enabling synthesis of model networks possessing defined pore size from any monomer polymerizable by ATRP. Introduction of an olefin moiety into the ATRP initiator enabled degradation of the materials by ozonolysis to yield star polymer products bearing three or four arms depending on which cross-linker was employed in the parent network. Size-exclusion chromatography of the ozonolysis products confirmed the pore size of the parent network and yielded insight into the number of unreacted functionalities. Model networks derived from a trifunctional alkyne were found to be more completely cross-linked than those derived from a tetrafunctional alkyne, presumably due to less steric hindrance in the former system.

Acrylates↗

Photochemical micropatterning of carbohydrates on a surface.

In this report, we demonstrate a versatile method for the immobilization and patterning of unmodified carbohydrates onto glass substrates. The method employs a novel self-assembled monolayer to present photoactive phthalimide chromophores at the air-monolayer interface. Upon exposure to UV radiation, the phthalimide end-groups graft to surface-adsorbed carbohydrates, presumably by a hydrogen abstraction mechanism followed by radical recombination to form a covalent bond. Immobilized carbohydrate thin films are evidenced by fluorescence, ellipsometry and contact-angle measurements. Surface micropatterns of mono-, oligo-, and polysaccharides are generated by exposure through a contact photomask and are visualized by condensing water onto the surface. The efficiency of covalent coupling is dependent on the thermodynamic state of the surface. The amount of surface-grafted carbohydrate is enhanced when carbohydrate surface interactions are increased by the incorporation of amine-terminated molecules into the monolayer. Glass substrates modified with mixed monolayers of this nature are used to construct carbohydrate microarrays by spotting the carbohydrates with a robot and subsequently illuminating them with UV light to covalently link the carbohydrates. Surface-immobilized polysaccharides display well-defined antigenic determinants for antibody recognition. We demonstrate, therefore, that this novel technology combines the ability to create carbohydrate microarrays using the current state-of-the-art technology of robotic microspotting and the ability to control the shape of immobilized carbohydrate patterns with a spatial resolution defined by the UV wavelength and a shape defined by a photomask.

Carbohydrates↗

Copper oxide nanocrystals.

It is well-known that inorganic nanocrystals are a benchmark model for nanotechnology, given that the tunability of optical properties and the stabilization of specific phases are uniquely possible at the nanoscale. Copper (I) oxide (Cu(2)O) is a metal oxide semiconductor with promising applications in solar energy conversion and catalysis. To understand the Cu/Cu(2)O/CuO system at the nanoscale, we have developed a method for preparing highly uniform monodisperse nanocrystals of Cu(2)O. The procedure also serves to demonstrate our development of a generalized method for the synthesis of transition metal oxide nanocrystals. Cu nanocrystals are initially formed and subsequently oxidized to form highly crystalline Cu(2)O. The volume change during phase transformation can induce crystal twinning. Absorption in the visible region of the spectrum gave evidence for the presence of a thin, epitaxial layer of CuO, which is blue-shifted, and appears to increase in energy as a function of decreasing particle size. XPS confirmed the thin layer of CuO, calculated to have a thickness of approximately 5 A. We note that the copper (I) oxide phase is surprisingly well-stabilized at this length scale.

Journal Article↗

Protein and bacterial fouling characteristics of peptide and antibody decorated surfaces of PEG-poly(acrylic acid) co-polymers.

The potential for base poly(ethylene glycol) graft poly(acrylic acid) PEG-g-PA copolymers and surface-modified PEG-g-PA materials to inhibit random protein fouling and bacterial adhesion are investigated. PEG-g-PA co-polymers were synthesized that inhibited non-specific protein and cellular adhesion. PEG-g-PA co-polymers were then covalently modified with either cell adhesion peptides (YRGDS, YEILDV) or fragments of antibodies to monocyte/macrophage integrin receptors (Anti-VLA4, Anti-beta1, Anti-beta2, and Anti-CD64) known to enhance macrophage adhesion and, perhaps, modulate their activation. Materials produced in this work were characterized using: hydrophobicity by contact angle; angle-resolved X-ray Photoelectron Spectroscopy to confirm the presence of PEG in the bulk material and the surface; degree of hydration; differential scanning calorimetry; and thermal gravimetric analysis. To evaluate the non-fouling efficacy of the various modified surfaces, three proteins, human serum albumin, human fibronectin (Fraction I) and human immunoglobulin were 125I labeled. Samples of base PEG-g-PA and PEG-g-PA, modified with various peptides, were exposed to solutions containing either 2 or 200 microg/ml of one of the labeled proteins at 37 degrees C for 24 h. PEG-g-PA substrata modified with directly bound peptides exhibited protein adsorption that varied depending upon the surface bounded peptide. PEG-g-PA modified with peptides linked by linear PEG tethers reduced protein adsorption at 24 h by approximately 45% in comparison to PEG-g-PA. Peptides linked by way of StarPEO and StarlikePEO tethers further decreased protein adsorption in comparison to PEG-g-PA. The ability of peptide:PEOtethers to inhibit protein adsorption appeared to be a function of type and surface coverage of the PEO tether and not influenced by the amount or molecular structure the tethered peptide. Peptides directly coupled to the PEG-g-PA increased the amount of protein fouling relative to controls and there appeared to be some dependency of the amount of protein adsorption on which peptide was tethered. Two 14C-labeled pathogens, Staphylococcus epidermidis and Pseudomonas aeruginosa, were used to quantify the degree of bacterial adhesion using two types of laminar flow cell chambers; one that provided invasive sampling of the target substrata and one that provided non-invasive microscopic surveillance of adhering bacterial cells. Attachment of both species to PEG-g-PA and peptide-modified PEG-g-PA was reduced compared to the basic poly(acrylic acid). Presence of peptides on the surface, whether directly bound or bound by the PEO tether did not influence adhesion of P. aeruginosa relative to controls. S. epidermidis adhesion rates increased slightly for those materials where peptides were directly bound to the surface but were reduced relative to base PEG-g-PA when peptides were bound by PEO tethers. All PEG-g-PA surfaces modified with fragments of monoclonal antibodies dramatically enhanced bacterial initial adhesion rates and maximum extent of attachment.

Acrylic Resins↗