Daniel Cappel

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The trypanothione synthetase (TryS) catalyses the two-step biosynthesis of trypanothione from spermidine and glutathione and is an attractive new drug target for the development of trypanocidal and antileishmanial drugs, especially since the structural information of TryS from Leishmania major has become available. Unfortunately, the TryS structure was(More)
DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzheimer's disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at(More)
3-D ligand conformations are required for most ligand-based drug design methods, such as pharmacophore modeling, shape-based screening, and 3-D QSAR model building. Many studies of conformational search methods have focused on the reproduction of crystal structures (i.e. bioactive conformations); however, for ligand-based modeling the key question is how to(More)
The model binding site of the cytochrome c peroxidase (CCP) W191G mutant is used to investigate the structural and dynamic properties of the water network at the buried cavity using computational methods supported by crystallographic analysis. In particular, the differences of the hydration pattern between the uncomplexed state and various complexed forms(More)
Predicting protein-ligand binding free energies is a central aim of computational structure-based drug design (SBDD)--improved accuracy in binding free energy predictions could significantly reduce costs and accelerate project timelines in lead discovery and optimization. The recent development and validation of advanced free energy calculation methods(More)
DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzhei-mer's disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at(More)
DYRK kinases are involved in alternative pre-mRNA splicing as well as in neuropathological states such as Alzheimer's disease and Down syndrome. In this study, we present the design, synthesis, and biological evaluation of indirubins as DYRK inhibitors with enhanced selectivity. Modifications of the bis-indole included polar or acidic functionalities at(More)
The protozoan parasites of the genus Trypanosoma sp. and Leishmania sp. are responsible for neglected diseases like Chagas' disease, African sleeping sickness or Leishmaniasis. The trypanothione synthetase (TryS) is an attractive new drug target for the development of trypanocidal and antileishmanial drugs [1]. In our virtual screening campaign for(More)
We describe a novel method to develop energetically optimized, structure-based pharmacophores for use in rapid in silico screening. The method combines pharma-cophore perception and database screening with protein ligand energetic terms computed by the Glide XP scoring function to rank the importance of pharmacophore features. We derive energy-optimized(More)
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