06-Sep-2010 - Wiley-VCH Verlag GmbH & Co. KGaA

Eclectic Enzymes

Easily Modified Building Blocks for Drug Design

In the pursuit of biologically active compounds, it is often necessary to be able to control the stereochemistry at predefined positions in a molecular skeleton. The search for ways to prepare chiral building blocks with known configuration that also show structural differentiation is important. Italian scientists working with Elisabetta Brenna have developed a technique to separate individual stereoisomers of building blocks that can be easily integrated into biologically active molecules. As the scientists from Politecnico di Milano, Milano, Italy, report in the European Journal of Organic Chemistry, their technique relies on the use of enzymes.

The specific activity of a biologically relevant molecule is often dependent on its stereochemistry (i.e., the spatial arrangement of its atoms). However, most compounds showing biological activity have complex structures, making their synthesis difficult. Moreover, compounds with differing stereochemistries can show different activities. Thus, it is sometimes desirable to prepare a range of compounds with the same structural backbone, but having different spatial arrangements of their atoms. The use of configurationally defined building blocks is attractive, but a method to obtain all the stereoisomers of a given building block is thus required.

Brenna and her colleagues have developed a method that allows a mixture of isomers to be differentiated, and it depends on the use of the enzyme lipase PS. The resolution of the stereoisomers relies on the preferential reaction of the enzyme with only one isomer, thereby creating a product mixture containing the desired compound and a mixture of the unreacted isomers. The desired product can be easily separated from the unreacted mixture, which can then be resubjected to the enzyme to undergo further differentiation. In this way, a wide range of building blocks with differing and known stereochemistries can be prepared.

The authors then showed the applicability of their method by incorporating their configurationally defined building blocks into biologically active compounds. Using simple and straightforward organic chemistry transformations, the authors were able to embed their building blocks into two classes of compounds that are of biological interest. Importantly, scientists can now easily examine the biological activities of all the different stereoisomers of a given compound. Thus, the Italian team is well on their way to helping scientists screen a diverse range of potential drugs that may lead to the treatment, cure, prevention, or diagnosis of diseases.

Original publication: Elisabetta Brenna et al.; "Oxygenated Stereotriads with Definite Absolute Configuration by Lipase-Mediated Kinetic Resolution: De Novo Synthesis of Imino Sugars and 6-Deoxy-C-glycosides"; European Journal of Organic Chemistry , 2010, No. 23, 4468–4475.

Facts, background information, dossiers
  • Italy
  • drug design
  • diseases
  • chiral building blocks
More about Wiley-VCH
  • News

    Chemical hydrogen storage system

    Hydrogen is a highly attractive, but also highly explosive energy carrier, which requires safe, lightweight and cheap storage as well as transportation systems. Scientists at the Weizmann Institute of Science, Israel, have now developed a chemical storage system based on simple and abundant ... more

    For a Better Contrast

    Magnetic resonance imaging (MRI) has emerged as one of the most powerful clinical imaging tools because of its superb spatial resolution and soft tissue contrast, especially when using contrast agents. In the European Journal of Inorganic Chemistry, scientists have presented a new kind of n ... more

    A Successful Coupling

    Coupled oxygen transfer and electron transfer reactions that use cofactors are enzymatic reactions of crucial significance to all lifeforms from bacteria to vertebrates. In the European Journal of Inorganic Chemistry, scientists have introduced a model for the enzyme sulfite oxidase. It is ... more

  • Companies

    Wiley-VCH Verlag GmbH & Co. KGaA

    Wiley-VCH publishes monographs, textbooks, major references works and journals in print or online. Wiley-VCH can look back on over 80 years of publishing in chemistry, materials sciences, physics and the life sciences. more

More about Politecnico di Milano
  • News

    Predicting unpredictable reactions

    Computational catalysis, a field that simulates and accelerates the discovery of catalysts for chemicals production, has largely been limited to simulations of idealized catalyst structures that do not necessarily represent structures under realistic reaction conditions. New research from t ... more

    Smog-eating graphene composite reduces atmospheric pollution

    Graphene Flagship partners the University of Bologna, Politecnico di Milano, CNR, NEST, Italcementi HeidelbergCement Group, the Israel Institute of Technology, Eindhoven University of Technology, and the University of Cambridge have developed a graphene-titania photocatalyst that degrades u ... more

    Short, Ultrashort, Sub-Cycle Short

    Ultrashort light pulses are a valuable achievement. They make it possible to observe chemical reactions, opening up the field of femtochemistry. Other current and/or future applications include high capacity telecommunications systems, photonic switching devices, optical coherence tomograph ... more