Angelica dahurica Extracts Improve Glucose Tolerance through the Activation of GPR119

Mokpo National University, Gachon University, Hanyang University, Gachon Medical Research Institute, South Korea; University of Bremen, Germany

Abstract

G protein-coupled receptor (GPR) 119 is expressed in pancreatic β-cells and intestinal L cells, and is involved in glucose-stimulated insulin secretion and glucagon-like peptide-1 (GLP-1) release, respectively. Therefore, the development of GPR119 agonists is a potential treatment for type 2 diabetes. In this publication,  screened 1500 natural plant extracts for GPR119 agonistic actions and investigated the most promising extract, that from Angelica dahurica (AD), for hypoglycemic actions in vitro and in vivo.

Electrospray ionization mass spectrometry (ESI-MS) data was measured using the Advion expression CMS

Pushing the Frontiers of Accessible Chemical Space to Unleash Design Creativity and Accelerate Drug Discovery

Learn how SpiroChem AG (Switzerland) utilized the Advion expression® Compact Mass Spectrometer (CMS) and Plate Express TLC Plate Reader for reaction monitoring and compound identification to aide in accelerating drug discovery.

Abstract:

In highly competitive research environments, the ability to access more complex structural spaces efficiently is a predictor of a company’s ability to generate novel IP-protected small molecule candidates with adequate properties, hence filling their development pipelines. SpiroChem is consistently developing new synthetic methodologies and strategies to access complex molecular structure, thereby facilitating and accelerating small molecule drug discovery. Pushing the limits of what are perceived as complex molecular structures allows SpiroChem and its clients to unleash creativity and explore meaningful chemical spaces, which are under-exploited sources of novel active molecules. In this article, we [SpiroChem] explain how we differentiated ourselves in a globalized R&D environment and we provide several snapshots of how efficient methodologies can generate complex structures, rapidly.

Rappsilber Laboratory, Insitute of Biotechnology, Technical University Berlin, Germany

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

A: The Rappsilber Laboratory is interested in studying the machinery of life, in particular protein structures and their interactions in living cells. Determining protein behaviour is crucial for developing new drugs or understanding terrible diseases such as cancer. We are doing this by developing state-of-the-art methods and new chemical tools for crosslinking mass spectrometry (crosslinking-MS), including new crosslinker reagents and crosslinking chemistry. Working on the chemistry-biology interface, our work encompasses chemical synthesis of peptides, fluorophore tagged sensors, peptide- and protein-reactive crosslinking reagents and bioorthogonal metal catalysts.

Q: WHAT WAS YOUR PREVIOUS WORKFLOW OR CHALLENGES?

A: This year (2020) we built a chemistry lab from scratch, here at the Institute of Biotechnology (TU Berlin). We had the opportunity to really think about our work flow requirements and create the most efficient chemical synthesis pipeline for a modern, 21st century, small chemistry laboratory. However, we are a satellite campus, located more than 10 km from the Institute of Chemistry, which meant that we were constrained by the lack of usual chemistry infrastructure. One of the major challenges that we faced here, is that without chemistry-specific analytical capability, we are working almost blind. Every step of chemical synthesis, including reaction monitoring, work-up, purification and final product characterisation required an exhausting and disruptive journey across Berlin!

Q: WHY DID YOU INCORPORATE THE EXPRESSION® CMS INTO YOUR LABORATORY?

A: We operate an advanced proteomics facility, with cutting edge, high-precision, high sensitivity mass spectrometers for analysing extremely complex peptide mixtures. But a chemist needs a workhorse, not a Formula 1 car. The Advion Interchim Scientific expression® CMS was a no-brainer. We needed a system that is versatile, compact, easy-to-use, easy-to-maintain (~10 minute calibration), robust and allows fast analysis (result in <30 seconds). This system is all of this, but furthermore it is a delight to use. The ASAP® Direct Analysis Probe works fantastically well for analysis of solids and liquids. Switching between APCI and ESI is so quick and easy. The Plate Express® system makes it a joy to identify reaction products directly from TLC plates, greatly simplifying subsequent purifications. The Plate Express™ also works really well for identifying synthesized peptides from TLC spots. The expression® CMS sits at the heart of our chemistry lab and workflow.

Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE EXPRESSION® CMS?

A: We would recommend the Advion Interchim Scientific expression® CMS to literally any research laboratory, big or small. The versatility of the system is truly impressive.

Leipzig University Medical School, Institute for Drug Discovery

 Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH? 

A: The research of the new Institute for Drug Discovery seeks to combine computational and experimental efforts to investigate proteins and their interactions with small molecule substrates. The Medicinal Synthetic Chemistry Core is part of the new institute and responsible for the synthesis of potentially bio-active compounds based on the computational results predicting a high binding affinity to the proteins’ active sites. 

Q: WHAT WAS YOUR PREVIOUS WORKFLOW OR CHALLENGES? 

A: Previously, we separated all unknown by-products of our synthesis in order to investigate their structure based on NMR and external mass spec service. This time wasting workflow often resulted in a dead-end strategy with low efficiency. 

Q: WHY DID YOU INCORPORATE THE expression® CMS INTO YOUR LABORATORY? 

A: Since the purchase of the CMS, we improved our strategic synthesis planning extraordinarily. By using Plate Express™ as TLC-Interface together with the expression® CMS, the by-products could become quickly separated on TLC-plates and directly analyzed by mass spectrometry afterwards. Now we see it, now we know it, and we get it quickly purified. 

Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE expression® CMS? 

A: I will highly recommend the CMS to all research institutes with a strong synthetical and natural product background of small molecules. 

Efficient Synthesis of Hydroxy-Substituted 2-Aminobenzo[d]thiazole-6-carboxylic Acid Derivatives as New Building Blocks in Drug Discovery

University of Ljubljana

Abstract

Benzo[d]thiazole is widely used in synthetic and medicinal chemistry, and it is a component of many compounds and drugs that have several different bioactivities. Herein, we describe an elegant pathway for synthesis of methyl 4- and 5-hydroxy-2-amino-benzo[d]thiazole-6-carboxylates as building blocks that can be substituted at four different positions on the bicycle and thus offer the possibility to thoroughly explore the chemical space around the molecule studied as a ligand for the chosen target. A series of 12 new compounds was prepared using the described methods and Williamson ether synthesis.

University of Minnesota, Therapeutics Discovery Development

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

We are the Institute for Therapeutics Discovery & Development. One of our main research core’s goals is the synthesis of biologically active small molecules with the additional goal of training the next generation of scientists through the Department of Medicinal Chemistry’s graduate student program. Our projects focus areas include contraception, cancer, infectious disease, and Alzheimer’s.

Q: WHAT WAS YOUR PREVIOUS WORKFLOW OR CHALLENGES?

A major headache for any synthetic chemist is the identification of the desired product when a mixture is obtained from a reaction. In the past, we would typically run a flash chromatography column, isolate spots of potential interest, concentrate them, and take 1H NMR, sometimes having to go back to column fractions as many as 4 times to analyze new spots if the first wasn’t desired product.

Q: WHY DID YOU INCORPORATE THE expression® CMS INTO YOUR LABORATORY?

Advion’s TLC–CMS system has streamlined our purification and analytical process significantly. What once took several hours to days to complete, we can now accomplish in as a little as 60 seconds. The Data Express software is also very easy to work with and has been quite useful in identifying adducts of our compounds.

Q: WHO WOULD YOU RECOMMEND TO PURCHASE THE expression® CMS?

We have been extremely happy with our Advion system and predict that it will quickly become a workhorse in any synthetic organic or medicinal chemistry laboratory.

Eberhard Karls University, Institute of Pharmaceutical Sciences, Tübingen, Germany

 

Q: WHAT IS THE FOCUS OF YOUR LAB’S RESEARCH?

A: We are a Medicinal Chemistry laboratory with a major focus on kinase inhibitors. Within the last decade, we have developed highly potent and selective chemical probes such as Skepinone L, a specific p38 MAP kinase inhibitor suitable for in vivo use. Our strategies involve the reversible targeting of kinases via ATP-competitive type I or less competitive type II inhibitors as well as intermediate type 11/2 inhibitors. More recently, we turned towards covalent kinase targeting by addressing non-catalytic cysteines. This strategy furnished excellent probes for JNK3 and JAK3. For example, we developed FM-381, an extremely isoform-selective JAK3 inhibitor, which is now available as a high-quality probe from the Chemical Probes Portal and the chemical probes program of the Structural Genomics Consortium.

Q: WHAT WAS YOUR PREVIOUS WORK EXPERIENCE?

A: Since our work mainly relies on organic synthesis, we have an urgent need for accurate and rapid characterization of novel compounds. While our group owns two NMR spectrometers and several HPLC systems, mass spectrometry was usually done at a shared service unit, which caused additional costs and delays. Although we were also equipped with several LC-MS devices, these were routinely used for biological samples or metabolism studies, thus adapting the workflows for chemical samples was always tedious. Consequently, a more practical solution was required.

Q: WHY DID YOU INCORPORATE THE EXPRESSION CMS INTO YOUR LABORATORY?

A: As mentioned, mass spectrometry was one of the bottlenecks in our synthesis endeavors. The purchase of an LC-MS system exclusively for reaction monitoring and compound analysis would have been an option. However, especially when dealing with crude mixtures, LC-MS devices are typically quite vulnerable and require a lot of maintenance. Moreover, if you do not have a UPLC system, LC-MS runs are time-consuming, limiting the number of samples to a maximum of a few dozens a day, which is a serious problem with respect to the size of our group.

Therefore, Advion’s expression CMS in combination with the Plate Express™ TLC plate reader was the perfect solution for us. It is easy to use, quite robust, offers a high throughput, and is suitable for almost the entire mass range of our compounds. Needless to say, the device is especially suited for reaction monitoring and the rapid assignment of product fractions from column chromatography.

Q: TO WHOM WOULD YOU RECOMMEND THE EXPRESSION CMS?

A: The expression CMS/Plate Express™ couple can be recommended to Organic or Medicinal Chemistry groups in general since it seamlessly integrates into organic synthesis workflows. Due to the affordable pricing, it is also a great solution for chemists in academia. Especially laboratories with high turnover of masters students and research interns will appreciate the robustness of the system.

The Role of Mass Spectrometry in the Drug Discovery Unit’s Workflow – Medicinal Chemistry & the Advion CMS

The Drug Discovery Unit at the University of Dundee is met daily with a global task: address unmet medical needs and diseases in the developing world, and continuously build their innovative targets portfolio.

Learn from Susan Davis, a Medicinal Chemist with the unit, how she has processed 22,639 sample injections via the Advion compact mass spectrometer, and how it has assisted her research daily.

Also hear from Dr. Jack Henion, Advion’s Scientific Founder, as he joins for a Q&A session about mass spec and it’s role in drug discovery and disease prevention. 

This webinar examines the workflow of a medicinal chemist as they utilize compact mass spectrometry techniques for drug discovery and disease prevention.