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Golden Spatula 2019

Winner of the Golden Spatula 2019

Werner Tabak

Fragment-Based Lead Discovery: Design and Synthesis of Arginase 1 Inhibitors, Avans University of Applied Sciences

This year, the Golden Spatula jury nominated Werner Tabak's thesis, written as part of his bachelor's degree in Food and Pharma at Avans University of Applied Sciences, for the 2019 Golden Spatula Award.

In his thesis, Werner describes the research he conducted at the Netherlands Translational Research Center in Oss. The research concerns the 11-step synthesis of an aliphatic boronic acid and the synthesis of fragments modeled on it. This boric acid is described in a patent as an arginase 1 inhibitor, and the NTRC has the technology to crystallize the arginase 1 protein. When this is done in the presence of the boric acid or one of the fragments, binding can be visualized and information about the interactions between the inhibitor and the protein can be obtained. Inhibition of arginase I is a promising strategy in the treatment of cardiovascular diseases, among others.

In a short, clear introduction, Werner demonstrates the relevance of the research and explains his choice of fragments. The reactions to be used are explained clearly and concisely, after which the research results are described in detail. In 11 steps that showcase modern organic chemistry, Werner produces boric acid with a total yield of 5.4%. This is no easy task, as the compound contains polar groups, which complicate purification. He also describes the choice of eight fragments and the subsequent syntheses and (2D) NMR and MS analyses of these fragments, some of which also contain highly polar groups.

After discussing the results of the protein crystallizations and biological tests, Werner draws conclusions about the necessary protein-ligand interactions and makes proposals for further research, thus bringing the report to a fitting conclusion.

Het verslag is verzorgd, voorzien van mooie illustraties en de beschrijving van de experimenten is van hoge kwaliteit. Daarbij maakt hij op een uitstekende wijze gebruik van de literatuur. Het hoge niveau van het onderzoek wordt bevestigd door de dagelijkse begeleider van Werner en de stagebegeleider. Bovendien wordt een gedeelte van het onderzoek binnenkort gepubliceerd in een wetenschappelijk tijdschrift.

Aan de hand van voornoemde feiten heeft de selectiecommissie geconcludeerd dat Werner een uitstekende kandidaat is voor nominatie voor de eerste plaats van de Gouden Spatel 2019.

De andere twee prijzen zijn toegekend aan:

Anouk Bosman - Hogeschool van Arnhem en Nijmegen
Microdevices with Macro Impact

Kielen Zuurbier - Hogeschool Utrecht
Development of a Novel Chemogenetically Inducible Gene Expression System for Controlled BDNF Overexpression by Endogenous B-cells as a Stroke Therapeutic