[person name=Matthijs J. van Lint picture=https://syborch.com/wp-content/uploads/2014/04/Foto-Thijssie.png pic_link=https://syborch.com/?p=278 title=”PhD Student” linkedin=”https://www.linkedin.com/in/matthijsvanlint” linktarget=”_blank”][/person]
|09/2011 – present|
|Phone:||+31 (0)20 59 87481|
Chemoenzymatic Synthesis And Molecular Probing Of Respiratory NADH Dehydrogenases
Complex I (NADH dehydrogenase) plays a central role in cellular energetics and is a major source of reactive oxygen species (ROS). It appears that tumour cells are closer to excessive ROS generation than healthy cells due to a more negative redox potential of the NAD(H) couple. Therefore, Complex I is an interesting target for differential drug design.
The most potent among the many structurally diverse inhibitors of Complex I are the annonaceous acetogenins, a large class of polyketide natural products isolated from the Annonaceae family of flowering plants. The typical structure of these compounds comprises of a (S)-5-methylbutenolide ring substituted at the 3-position with a long linear aliphatic chain incorporating often two tetrahydrofuran (THF) fragments (e.g. compounds 1, 2 and 3).
We envision that the bis-THF-bis-epoxides 4 can be synthesized stereo¬selectively from meso-epoxides 5 by biocatalytic hydrolysis, using a broad range of epoxide hydrolases from the collection hosted at the University of Graz.
 Lenaz et al., Biochim Biophys Acta 2009, 1787, 384–392
 Manda et al., Curr. Chem. Biol. 2009, 3, 342-366
 Westerhoff, Systems Biology: New Paradigms for Cell Biology and Drug Design, Springer Berlin Heidelberg, 2007, 45-67. Print
 McLaughlin, J. Nat. Prod. 1999, 62, 504-540
 Faber et al. Eur. J. Org. Chem. 2001, 4537-4542