Cancer researchers are focusing their efforts on identifying central pathways that trigger or enhance the invasiveness of tumor cells. One such target is EMMPRIN (...
Cancer researchers are focusing their efforts on identifying central pathways that trigger or enhance the invasiveness of tumor cells. One such target is EMMPRIN (Extracellular Matrix Metalloproteinase Inducer). It has been shown that EMMPRIN expression is linked to various cell signaling pathways that lead to an increase in tumor cell vascularization. Researchers are focusing efforts on elucidating the role of EMMPRIN in a number of disorders including cancer, arthritis, tissue repair and numerous inflammation-dependent diseases. DESCRIPTION/DETAILS Basigin is a member of the immunoglobulin superfamily thatis also known as EMMPRIN. Human basigin is expressed as two differentiallyspliced isoforms encoded by a single gene found on chromosome, renamedrespectively as basigin-1 and basigin-2. Attempts to demonstrate specifichemophilic on separate cells, or between soluble forms of recombinant basiginusing surface Plasmon resonance have not been successful, suggesting thatbasigin-2 cannot function as a receptor for itself. In order to identify possible receptors for soluble basiginligand, an affinity purification approach was employed. This approach resulted inthe labeling of several potential interacting proteins, and MALDI MS/MSsequencing of one of these proteins identified a novel isoform of human basigin(basigin-3).
Immunoprecipitation studies using cell fractions revealed thatrBSG interacts with basigin-2 at the cell membrane, and subsequently interactswith the basigin-3 isoform within the cell. Small-interfering RNA (siRNA)knockdown of basigin-2 protein reduced, but did not eliminate, rBSG-mediatedERK activation in HESCs, suggesting that additional cell surface receptors forsoluble basigin may exist. Taken together, these results support the hypothesisthat basigin-2 can function as a receptor for soluble basigin and demonstratethat the hemophilic interactions between basigin proteins are not dependentupon glycosylation of the basigin ligand. It has also been shown that soluble EMMPRIN binds tomembrane-bound EMMPRIN and the bound complex is internalized presenting apotential means to deliver therapeutic compounds to the cell in a highlytargeted manner. A therapeutic scheme isproposed that aims to design EMMPRIN-conjugates designed to deliver cancertherapeutics in a targeted fashion.
Conjugation oftherapeutics to EMMPRIN increases specificity and targets cancers cells cancer (skin, bladder,breast); other inflammatory diseases (arthritis, endometriosis); Upregulationof inflammatory response.
It is possible to design therapeutic agents directed toward human basigin. Possible therapeutic scheme to block tumor progressionor inflammation.
Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with...
Liquid chromatography/mass spectrometry (LC/MS) is increasingly being used for metabolic analysis due in part to its widespread availability and compatibility with biological samples. This invention provides ionizable, isotopic labeling reagents and labeling reaction products, answering the current need for relative quantification using mass spectrometry.
Absolute quantification of an analyte relies upon the addition of an internal standard differing only in its isotopic form. However, it is impractical to add an isotopic standard for every compound when performing more comprehensive metabolic profiling. Relative quantification between samples is more amenable to analyzing broad classes of compounds, and it often provides very useful biological information.
Heavy and light isotopic forms of methylacetimidate have been synthesized and used as labeling reagents for quantification of amine-containing molecules, such as biological samples. Heavy and light isotopic forms of formaldehyde and cholamine have also been synthesized and used independently as labeling reagents for quantification of amine-containing and carboxylic acid-containing molecules, such as these found in biological samples. Advantageously, the labeled end-products are positively charged under normal acidic conditions involving conventional liquid chromatography mass spectrometry (LC/MS) applications.
This invention improves the precision of relative quantification by minimizing or negating errors associated with run-to-run irreproducibility. Such errors can arise from variations in mass spectrometric detection sensitivity, such as those caused by ionization suppression in electrospray, or from retention time differences between runs. The isotopic pair of labeled compounds co-elute within a single run. Therefore, they have identical retention times and are electrosprayed from identical solution conditions.
Dr. van der Donk has developed a screening system for identifying novel antibiotics. The system uses phage display and has been optimized for lantibiotic natural...
Dr. van der Donk has developed a screening system for identifying novel antibiotics. The system uses phage display and has been optimized for lantibiotic natural products. The system also has utility for investigating interactions between lantibiotics and other peptides. Lantibiotics have complex structures which make them particularly stable under changing pH and protease exposure as well as possessing the ability to bind to bacterial cell wall targets. This makes them ideal for scaffolds for new antibiotic discovery that can combat the burgeoning problem of antibiotic resistance
The invention provides a silica nanoparticle comprising a non-porous matrix of silicon-oxygen bonds, wherein the matrix comprises organic agents conjugated to...
The invention provides a silica nanoparticle comprising a non-porous matrix of silicon-oxygen bonds, wherein the matrix comprises organic agents conjugated to silicon or oxygen atoms in the matrix, the organic agents are conjugated to the matrix through linker L groups, wherein the linker L comprises, for example, an ester, urea, thiourea, or thio ether group, and wherein the diameter of the nanoparticle is about 15 nm to about 200 nm. The invention also provides novel methods of making and using the silica nanoparticles.
Dr. Zimmerman's lab has developed a series of bioactive compounds for the treatment of myotonic dystrophy. The compounds disrupt the MBNL-(CUG) foci in vivo and...
Dr. Zimmerman's lab has developed a series of bioactive compounds for the treatment of myotonic dystrophy. The compounds disrupt the MBNL-(CUG) foci in vivo and partially rescue the missplicing of cTNT and IR mRNAs. These novel compounds, utilizing bisamidinium-based inhibitors, show a 1000-fold greater inhibition potency than a previous compound and are able to degrade the causative agent of the disease.
Dr. Metcalf and Dr. van der Donk from the University of Illinois have discovered 12 novel phosphonate natural products as well as the genes responsible for the...
Dr. Metcalf and Dr. van der Donk from the University of Illinois have discovered 12 novel phosphonate natural products as well as the genes responsible for the biosynthesis of hundreds of additional compounds of other natural product classes. Phosphonic and phosphinic acids represent an underexploited group of bioactive compounds with great promise for the treatment of human disease.