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In an article just published in the journal Nature Nanotechnology, several University of Delaware researchers show how a new peptide-based hydrogel could one day make that reconnection process easier to perform and less likely to fail. The new process uses a hydrogel developed by Daniel J. Smith, who earned his doctorate at UD in 2013 and is the lead author of the article. Other collaborators include Katelyn Nagy-Smith, who has recently completed all requirements for her doctorate at UD, and Joel Schneider, who was a professor at UD and now is in the Chemical Biology Laboratory at the National Cancer Institute. Also part of the study were researchers from Johns Hopkins University School of Medicine and the Department of Electrical and Computer Engineering at Johns Hopkins. Smith designed the peptide, building on a self-assembling process developed more than a decade ago by Schneider while he was a professor in UD's Department of Chemistry and Biochemistry, and Darrin Pochan, professor and chair of UD's Department of Materials Science and Engineering. Nagy-Smith did the microscopy, using a transmission electron microscope at the National Cancer Institute to show how the fibers change when exposed to ultraviolet light. The way tiny vessels are reconnected now includes stitches applied in microsurgery. But the tiny, thin-walled vessels are fragile and prone to damage in handling. The peptide-based hydrogel can be tuned in precise ways with a specific amino acid, allowing the material to change form several times during a procedure - becoming rigid enough to open and support a tiny vessel when first injected and then, after the sutures are complete, dissolving quickly under ultraviolet light to allow restored circulation. Smith placed the amino acid into the sequence in a way that allows precise control and found the hydrogel would form a semi-solid to support the walls of the tiny vessel, preventing damage during the suturing while also suspending the ends for better control. "It's analagous to Lego blocks putting themselves together to build a structure, then breaking down when told to do so," said Smith, who now works at Glaxo Smith Kline. "There are attractive forces at work - these are hydrophobic, greasy molecules that want to associate together, but can also be triggered to come apart." So, he said, when the substance is injected into the ends of the tiny vessel, the excess oozes out of the ends forming a small mass of gel that surrounds both ends, allowing surgeons to make an easier connection. "This would help in any type of surgery where you are trying to restore as many vessels as you can, whether in a whole transplant or in damaged tissue from some kind of accident," Nagy-Smith said. "It not only holds the vessel open, it actually sticks vessels in place without using a lot of clamps. The surgeon essentially has a third hand." Tested with mice, whose femoral arteries are about 200 microns in diameter - four or five human hairs - the paper shows the precise process used by the collaborators and suggests the hydrogel could one day be used in cardiac bypass and transplant surgeries and also could open up new possibilities in research.

Yoshida J.,Chemical Biology Laboratory | Yoshida J.,Iwate Medical University | Ito Y.,Iwate University | Nakano T.,Iwate University | And 6 more authors.
Journal of Agricultural and Food Chemistry | Year: 2013

A new biological activity of falcarindiol isolated from Japanese parsley (Oenanthe javanica) using the mutant yeast YNS17 strain (zds1Δ erg3Δ pdr1Δ pdr3Δ) was discovered as an inhibitor of glycogen synthase kinase-3β (GSK-3β). Falcarindiol inhibited GSK-3β in an ATP noncompetitive manner with a Ki value of 86.9 μM using a human enzyme and luminescent kinase assay platform. Falcarindiol also both suppressed gene expression of glucose-6-phosphatase (G6Pase) in rat hepatoma H4IIE cells and protected mouse neuroblastoma HT22 cells from glutamate-induced oxidative cell death at 10 μM. During an oral glucose tolerance test (OGTT), the blood glucose level was significantly decreased in the rats treated with oral administration of O. javanica extract containing falcarindiol (15 mg/kg). These findings indicate that Japanese parsley could be a useful food ingredient against type-2 diabetes and Alzheimer's disease. © 2013 American Chemical Society.

Thomas J.D.,Chemical Biology Laboratory | Cui H.,U.S. National Cancer Institute | North P.J.,U.S. National Cancer Institute | Hofer T.,U.S. National Cancer Institute | And 2 more authors.
Bioconjugate Chemistry | Year: 2012

We have previously described an approach whereby antibody Fc fragments harboring a single C-terminal selenocysteine residue (Fc-Sec) are directed against a variety of targets by changing the peptide or small molecule to which they are conjugated. In the present work, we describe methodology for improving the efficacy of these Fc-Sec conjugates by incorporating cytotoxic drugs. The Fc-Sec protein is first programmed to target specific tumor cell types by attachment of a bifunctional linker that contains a "clickable" handle (e.g., cyclobutane or cyclooctyne) in addition to a tumor cell-binding peptide or small molecule. Following Fc-Sec conjugation, a cytotoxic warhead is then attached by cycloaddition reactions of tetrazine or azide-containing linker. To validate this approach, we used a model system in which folic acid (FA) is the targeting moiety and a disulfide-linked biotin moiety serves as a cytotoxic drug surrogate. We demonstrated successful targeting of Fc-Sec proteins to folate-receptor expressing tumor cells. Tetrazine ligation was found to be an efficient method for biotin "arming" of the folate-targeted Fc-Sec proteins. We also report novel bioconjugation methodologies that use [4 + 2] cycloaddition reactions between tetrazines and cyclooctynes. © 2012 American Chemical Society.

Singh S.,Chemical Biology Laboratory | Singh M.K.,Banaras Hindu University | Agarwal A.,Banaras Hindu University | Awasthi S.K.,Chemical Biology Laboratory
Acta Crystallographica Section E: Structure Reports Online | Year: 2011

The title compound, C 15H 9ClO 2, is a synthetic flavonoid obtained by the cyclization of 3-(4-chloro-phen-yl)-1-(2-hy- droxy-phen-yl)prop-2-en-1-one. The 4-chloro-phenyl ring is twisted at an angle of 11.54°with respect to the chromen-4-one skeleton. In the crystal, pairs of molecules are interconnected by weak Cl⋯Cl interactions [3.3089 (10) Å] forming dimmers which are further peripherally connected through intermolecular C-H⋯O hydrogen bonds..

Kumar C.G.,Chemical Biology Laboratory | Mongolla P.,Chemical Biology Laboratory | Basha A.,Chemical Biology Laboratory | Joseph J.,Chemical Biology Laboratory | And 2 more authors.
Journal of Microbiology and Biotechnology | Year: 2011

Methyl violet, used extensively in the commercial textile industry and as a biological stain, is a hazardous recalcitrant. Aspergillus sp. strain CB-TKL-1 isolated from a water sample from Tsumoriri Lake, Karzok, Ladakh, India, was found to completely decolorize methyl violet within 24 h when cultured under aerobic conditions at 25°C. The rate of decolorization was determined by monitoring the decrease in the absorbance maxima of the dye by UV-visible spectroscopy. The decolorization of methyl violet was optimal at pH 5.5 and 30°C when agitated at 200 rpm. Addition of glucose or arabinose (2%) as a carbon source and sodium nitrate or soyapeptone (0.2%) as a nitrogen source enhanced the decolorization ability of the culture. Furthermore, the culture exhibited a maximum decolorization rate of methyl violet after 24 h when the C:N ratio was 10. Nine N-demethylated decolorized products of methyl violet were identified based on UV-visible spectroscopy, Fourier transform infrared (FTIR), and LC-MS analyses. The decolorization of methyl violet at the end of 24 h generated mono-, di-, tri-, tetra-, penta-, and hexa-N-demethylated intermediates of pararosaniline. The variation of the relative absorption peaks in the decolorized sample indicated a linear decrease of hexa-N-demethylated compounds to non-N-demethylated pararosaniline, indicating a stepwise N-demethylation in the decolorization process. © The Korean Soceity for Microbiology and Biotechnology.

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