Konstanz-based MCAT GmbH is focused on the development and production of azido-PEG glycosides, carbohydrate structures that can be used for a broad range of different applications, including the functionalisation of surfaces, the derivatisation of drugs and other compounds as well as the production of multivalent lectin ligands.
Azido-polyethylene glycol (azide-PEG) glycosides are carbohydrate compounds that are linked to an azide by way of a polyethylene glycol (PEG) residue. Such compounds can be used for a broad range of applications such as the functionalisation of surfaces and solid phases and also the derivatisation of drugs, which makes them popular substances for the pharmaceutical industry. “These compounds improve the drugs’ solubility in water and increase their ability to enter cells, thereby having a positive effect on drug uptake,” said Dr. Magnus Schmidt, Head of Research and Marketing at MCAT GmbH. Derivatisation is of great interest for the pharmaceutical industry, as it enables the transformation of existing drugs into new drugs (derivatives) that are more effective or better tolerated by patients. A derivative is a substance produced by transforming a chemical compound into a product of similar chemical structure, but with improved properties. For example, acetylsalicylic acid (Aspirin) is derived from salicylic acid, which is the medically active compound.
Azido-PEG glycosides are also used as building blocks for the synthesis of multivalent lectin ligands. Lectins are proteins that recognise and bind carbohydrates; they play a role in the recognition of cells. They usually possess several carbohydrate-specific binding sites. A molecule that contains several binding sites for carbohydrate units is referred to as multivalent. “Lectin ligands produced from azido-PEG glycosides have the potential to be used one day in the future for the treatment of toxic effects resulting from the consumption of plants such as uncooked beans, which are difficult to digest and can cause adverse reactions. This is made possible as the lectin ligands are able to bind certain plant lectins that cause such toxic reactions,” said Schmidt.
Azido-PEG glycosides might also be used for the development of drugs to treat chronic inflammatory disorders. It is known that interactions between carbohydrates and lectins (in this case selectins, which also bind to sugar moieties) play a major role in inflammatory processes. A multivalent drug has the potential to inhibit such processes, thus counteracting inflammation. MCAT GmbH has optimised the production processes for the synthesis of carbohydrate derivatives, including modifying their laboratory infrastructure and developing and introducing alternative purification steps. In addition, MCAT GmbH purchased an NMR device in autumn 2011 that enables the company to accurately examine the products (analytics and quality control). “We are already able to produce a broad range of different azido-PEG glycosides in such a way that saves resources. We are able to re-isolate and re-use leftover reaction substances,” said Schmidt.
Azido-PEG glycosides can be used to functionalise surfaces. This is made possible through the (2+3) Huisgen cycloaddition, which is named after Rolf Huisgen and was referred to as the “cream of the crop” of click chemistry by Karl Barry Sharpless in 2001. Nowadays, the term click chemistry describes a reaction between two partners that has a short reaction time and high yields. Cu(I)-catalysed and copper-free (which involves cyclo-octines) click reactions are used to immobilise molecules on surfaces and produce molecule derivatives and multivalent lectin ligands.
Azido-PEG glycosides can be easily and rapidly immobilised by chemical ligation on a surface that has been functionalised with alkines. These surfaces can then be used to investigate the interactions between carbohydrates and other biomolecules. The use of state-of-the-art molecular biology analysis systems such as microarrays enables the interaction between carbohydrates and proteins to be examined, to cite just one example. “This can also be done with enzyme-coupled lectin binging tests (ELLA; see figure). Both tests require carbohydrates to be immoblised on a surface prior to analysis,” Schmidt added.
MCAT GmbH supports its clients in the selection of suitable compounds. The company can also be commissioned for individual contract development. “The technology further developed and used by MCAT is based on reaction mechanisms that have been known for many years in the field of carbohydrate chemistry, but which are difficult to use successfully for the production of complex carbohydrate structures,” Magnus Schmidt said. Progress made over the last two years in the field of life science technologies has helped MCAT GmbH to establish a new field of operation, which enables the company to tap into new markets and consolidate its position in existing markets. Manufacturers and laboratories active in the pharmaceutical and polymer industries find it a lot easier and cheaper to rely on MCAT GmbH’s services rather than producing the building blocks themselves.
MCAT GmbH, which was spun out of the University of Konstanz in 1998, has been continuously expanding its life sciences services since its inception. The company also offers services related to the development and production of catalysts and metalorganic compounds. MCAT GmbH supports its clients in their search for suitable catalyst systems; it produces these systems and also carries out all steps according to cGMP standards if required. Using asymmetric catalytic processes, the company produces enantiomers, i.e. molecules that are mirror images of each other and non-superimposable. Over the last few years the purity of enantiomers has become increasingly important in the production of pharmaceutical compounds. “For example, chiral drugs are nowadays produced in enantiopure form, as regulatory authorities require separate pharmacological and pharmacokinetic proof that the enantiomers have identical levels of pharmacological activity," said Dr. Magnus Schmidt.
MCAT GmbHHead of Research and MarketingDr. Magnus SchmidtHermann-von-Vicari-Str. 2378464 KonstanzFax: +49 (0)7531/ 939 098Mobile: +49 (0)174/ 24 65 904E-mail: schmidt(at)mcat.de