A: My research focuses on developing small molecule modulators to pharmacologically validate potential antibiotic, cancer, and chronic pain therapeutic targets.
Q: WHAT WAS YOUR PREVIOUS WORKFLOW AND SOME OF THE CHALLENGES YOU EXPERIENCED?
A: Purdue’s campus has not had easy access to walk-up mass spec instruments. To get reliable mass spec data for small molecules, one would typically have to submit a request to a central mass spec core. This was not conducive to reaction monitoring or small molecule characterization.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: The university research office acknowledged this need and purchased three CMSL instruments with the Plate Express™ and ASAP® capability for walk-up mass spec at three locations on campus. This provided easy access to mass spec data to monitor reactions and characterize molecules. We have even confirmed covalent modification of a protein with a small molecule ligand using this instrument. I was so impressed with the user-friendly interface and instrument set up, that I applied for and received a grant to purchase a 4th instrument to be used in the undergraduate organic teaching lab in the course I teach. We have now incorporated this instrument into the workflow of lab modules for students to collect and analyze their own mass spec data. Something else that stuck out as a positive with Advion is that the data processing software, Data Express™, is free to download for any user. We can have our students analyze data off-site on their own computers. We look forward to incorporating this instrument into more organic lab modules and other courses.
Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION®CMS?
A: I recommend this instrument for both research labs and teaching labs. The ASAP® probe is especially convenient and easy to use for mass spec data.
Q: DO YOU HAVE ANY PUBLICATIONS OR PRESENTATIONS USING THE EXPRESSION®CMS?
A: Not yet, but we have one in review for my research, and another that will be written to publish the laboratory module in the Journal of Chemical Education.
The Touch Express™ Open Port Sampling Interface (OPSI), is designed for simple sampling of solids, liquids and sample preparation tips and fibers. The novel ambient sampling technique was developed by Gary Van Berkel and Vilmos Kertesz, of Oak Ridge National Laboratory.
Paired with the electrospray ion source of the expression® Compact Mass Spectrometer, the product incorporates a low volume, open port of continuously swept solvent, flowing directly into the electrospray ion source of the mass spectrometer.
During this webinar you will:
Learn how any soluble material touching the port is analyzed by the expression® Compact Mass Spectrometer in just seconds.
Learn how the sample technique eliminates sample preparation and provides zero carry over.
Find fast analysis methods for solids, liquids and sample preparation tips and fibers.
Claudia Schmidt, Bianka Karge, Rainer Misgeld, Aram Prokop, Mark Brönstrup,Ingo Ott
A series of gold(I) complexes with two N-heterocyclic carbene ligands (biscarbene gold complexes) were prepared and evaluated for their effects against cancer cells and pathogenic bacteria. Proliferation inhibition was observed in cancer cells and in Gram-positive bacteria, whereas Gram-negative bacteria were less sensitive towards the compounds. The protein binding and cellular uptake were quantified and the combined results indicated a strong correlation between cellular bioavailability and antiproliferative effects. The biscarbene gold complexes inhibited bacterial and mammalian TrxRs with low to moderate potency. However, based on the obtained structure–activity-relationships and the high cellular accumulation levels, TrxR inhibition can be considered as a relevant contributor to the cellular pharmacology of biscarbene gold(I) complexes.
The MS analysis was carried out using Advion Expression® CMS.
Michael Lückmann, Roxana-Maria Amarandi, Natalia Papargyri, Mette H. Jakobsen, Elisabeth Christiansen, Lars J. Jensen, Aurel Pui, Thue W. Schwartz, Mette M. Rosenkilde, Thomas M. Frimurer
The human cytomegalovirus-encoded G protein-coupled receptor US28 is a constitutively active receptor, which can recognize various chemokines. Despite the recent determination of its 2.9 Å crystal structure, potent and US28-specific tool compounds are still scarce. Here, we used structural information from a refined US28:VUF2274 complex for virtual screening of >12 million commercially available small molecule compounds. Using a combined receptor- and ligand-based approach, we tested 98 of the top 0.1% ranked compounds, revealing novel chemotypes as compared to the ~1.45 million known ligands in the ChEMBL database. Two compounds were confirmed as agonist and inverse agonist, respectively, in both IP accumulation and Ca2+mobilization assays. The screening setup presented in this work is computationally inexpensive and therefore particularly useful in an academic setting as it enables simultaneous testing in binding as well as in different functional assays and/or species without actual chemical synthesis.
The LC/MS analysis was carried out using Advion Expression® CMS.
A series of four thiosemicarbazones from 6-nitropiperonal along with the corresponding copper complexes were synthesized. The biophysical characteristics of the complexes were investigated by the binding to DNA and human serum albumin. The binding to DNA is moderate; the binding constants run from (0.49–7.50) × 104 M− 1. In relation to HSA, the complexes interact strongly with binding constants on the order of 105 M− 1. The complexes also display antioxidant behavior as determined by the ability to scavenge diphenylpicrylhydrazyl (dpph) and nitric oxide radicals. The antimicrobial profiles of the compounds, tested against a panel of microbes including five of the ESKAPE pathogens (Staphylococcus aureus, MRSA, Escherichia coli, Klebsiella pneumoniae, MDR, Acinetobacter baumannii, Pseudomonas aeruginosa) and two yeasts (Candida albicans and Cryptococcus neoformans var. grubii), are also described. The compounds contain a core moiety that is similar to oxolinic acid, a quinolone antibiotic that targets DNA gyrase and topoisomerase (IV). The binding interaction between the complexes and these important antibacterial targets were studied by computational methods, chiefly docking studies. The calculated dissociation constants for the interaction with DNA gyrase B (from Staphylococcus aureus) range from 4.32 to 24.65 μM; the binding was much stronger to topoisomerase IV, with dissociation constants ranging from 0.37 to 1.27 μM.
The MS analysis was carried out using Advion Expression® CMS.
Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH? A: New Path Molecular Ltd is focused on the development and implementation of high performance enabling technologies to assist the chemical and pharmaceutical industries. We develop and implement solutions for customers who are looking to develop or improve chemical steps or routes utilizing state of the art technologies.
Q: WHAT WAS YOUR PREVIOUS WORKFLOW AND EXPERIENCED CHALLENGES?
A: Previously we only had access to mass spectrometry facilities through an external vendor. Whilst these were first class, analysis was slowed as the facilities were not on site.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: Within a small but expanding group the expression® CMS meets our requirements for an instrument that is intuitive to use, robust and capable of being maintained, expanded and serviced without manufacturer call outs. The expression® CMS combines solid performance at a reasonable price and without excessive maintenance costs. For us the instrument is ideal for day to day laboratory analysis.
Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION® CMS?
A: All chemists looking for a robust easy to use mass spectrometer that does not require extensive work to keep the instrument in service and that will give solid performance in day to day laboratory analysis tasks.
Advion Interchim Scientific’s range of AVANT®, high performance, liquid chromatography systems can be used standalone with UV and UV/Vis detector options, or with the expression® compact mass spectrometer to provide seamlessly integrated LC/CMS under the full control of Advion Interchim Scientific’s simple, intuitive Mass Express software suite.
Modular, stackable design, with many options, provides custom solutions for both HPLC and UHPLC needs. From the simplest manual injection HPLC to a fully automated, streamlined UHPLC system and everything in-between, the AVANT® series can be configured to fit your analytical requirements and your budget.
A: My research at the Biomedical Research Imaging Center (BRIC) focuses on the development and validation of novel radiolabeling methods and multimodality molecular imaging probes for various diseases, including cancer, diabetes, neuro-disease, and cardio vasculature disease. To be more specific, the major efforts of my current research include: 1) developing novel radiochemistry for cancer diagnosis, neuroimaging, cardiac imaging, diabetic research, drug discovery and development, and targeted radionuclide therapy; 2) developing multimodality molecular imaging agents; 3) developing novel nanotechnology and studying its biomedical applications; 4) developing pre-targeted drug delivery system for cancer imaging and therapy; and 5) performing PET related translational research.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: Sometimes we have a reaction, and we do not know which peak contained the product, so we send the sample to the mass spectrometry facility to be analyzed. Additionally, there are times when we have 10-20 peaks, and it is impossible to collect them all to be sent.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: The convenience of having a mass spectrometer in our laboratory means that we can increase working efficiencies by not waiting 2-3 days for results from the LC lab. The expression® CMS is a good system for routine analysis.
Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION® CMS?
A: I recommend the expression® CMS to any traditional organic and radiochemistry laboratory. I am impressed by the smaller size and by how simple it is to operate. We were able to use it quickly.
Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH? A: In our Department of Medicinal Chemistry we have focus on the synthesis of novel molecules with biological activity. We synthesize molecules of natural origin, peptides and heterocyclic compounds. As integral part of the department’s work we also do drug analysis.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: The modern Faculty of Pharmacy provides state-of-the art analytical techniques. We have a 400 MHz NMR in our department and access to 600 MHz and 800 MHz NMRs in the Infrastructural Centre. Furthermore, we routinely use FT IR, DAD HPLC. At one point biggest bottleneck was MS, as we had access to HRMS, but we did not have MS in our department for routinely use in synthesis and analytical procedures.
Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?
A: We thought that a robust, easy to use MS would be most useful in our laboratory to make our work faster and most efficient. Versatile use, simple use of various ion sources, and direct application of samples from TLC or use of dissolved samples, were possibilities which persuaded us.
Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION® CMS?
A: We would recommend the expression® CMS to every medicinal chemistry department, who would use MS in a daily routine from undergraduate students to post-docs. Doing MS analysis is now a common and integral part of our work as well as doing TLC-MS-coupling with the Plate Express™. It is an excellent way for entry level to mass spectrometry, because of simple use, robustness and good results of analysis.
A: My group are actively researching the application of mass spectrometry to a range of problems in both chemical and biomedical science. In particular we are involved in the application of mass spectrometry based proteomics for label free quantitation of proteins from human tissue samples and also in the identification of trace analytes from environmental samples. We are also investigating the synthesis of novel co-polymeric monolithic phases for sample extraction and separation.
Q: WHAT WAS YOUR PREVIOUS WORK FLOW OR CHALLENGES?
A: The Chemistry Department at Hull have long recognised the need for practical training on a wide range of chemical instrumentation. In particular we recognise the requirement from many companies in the pharmaceutical and fine chemical sectors for practical training in GC/MS and LC/MS. The Advion expressionL compact mass spectromater (CMS) was purchased to provide such training at an undergraduate level and has been incorporated into the range of instrumental analysis practicals for final year students. The expressionL CMS fits tidily on the bench-top next to the HPLC system and gives students the chance experience at first hand the use of LCMS as an analytical technique. The ease of use and robust nature of the system means that the expressionL CMS lends itself to the undergraduate laboratory where users will not be experts in mass spectrometry at this point in their careers.
Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?
A: We use the expressionL CMS to give undergraduate students practical experience of using LC/MS to prepare and analyse a ‘mock’ urine sample. The sample has to be prepared by adding the internal standard and extracting the analytes using Solid Phase Extraction (SPE) to obtain a sample suitable for LC/MS analysis. The aim is to identify and quantify the compounds found in the sample by reference to the internal standard added. The HPLC separation is a rapid 10 min gradient elution and the ability to incorporate the data from the UV detector into the MS data provides an additional benefit. Purchasing the expression L CMS has allowed us to provide practical training in LC/MS for our undergraduate students at a time when prospective employers are actively seeking such skills.
