0000000001303981
AUTHOR
Matthias Rottmann
showing 6 related works from this author
Tuning and Predicting Biological Affinity: Aryl Nitriles as Cysteine Protease Inhibitors
2012
A series of aryl nitrile-based ligands were prepared to investigate the effect of their electrophilicity on the affinity against the cysteine proteases rhodesain and human cathepsin L. Density functional theory calculations provided relative reactivities of the nitriles, enabling prediction of their biological affinity and cytotoxicity and a clear structure-activity relationship.
Optimization of Triazine Nitriles as Rhodesain Inhibitors: Structure-Activity Relationships, Bioisosteric Imidazopyridine Nitriles, and X-ray Crystal…
2013
The cysteine protease rhodesain of Trypanosoma brucei parasites causing African sleeping sickness has emerged as a target for the development of new drug candidates. Based on a triazine nitrile moiety as electrophilic headgroup, optimization studies on the substituents for the S1, S2, and S3 pockets of the enzyme were performed using structure-based design and resulted in inhibitors with inhibition constants in the single-digit nanomolar range. Comprehensive structure-activity relationships clarified the binding preferences of the individual pockets of the active site. The S1 pocket tolerates various substituents with a preference for flexible and basic side chains. Variation of the S2 subs…
Use of poly(amidoamine) drug conjugates for the delivery of antimalarials to Plasmodium
2013
Current malaria therapeutics demands strategies able to selectively deliver drugs to Plasmodium-infected red blood cells (pRBCs) in order to limit the appearance of parasite resistance. Here, the poly(amidoamines) AGMA1 and ISA23 have been explored for the delivery of antimalarial drugs to pRBCs. AGMA1 has antimalarial activity per se as shown by its inhibition of the in vitro growth of Plasmodium falciparum, with an IC50 of 13.7 μM. Fluorescence-assisted cell sorting data and confocal fluorescence microscopy and transmission electron microscopy images indicate that both polymers exhibit preferential binding to and internalization into pRBCs versus RBCs, and subcellular targeting to the par…
(Approximate) Low-Mode Averaging with a new Multigrid Eigensolver
2015
We present a multigrid based eigensolver for computing low-modes of the Hermitian Wilson Dirac operator. For the non-Hermitian case multigrid methods have already replaced conventional Krylov subspace solvers in many lattice QCD computations. Since the $\gamma_5$-preserving aggregation based interpolation used in our multigrid method is valid for both, the Hermitian and the non-Hermitian case, inversions of very ill-conditioned shifted systems with the Hermitian operator become feasible. This enables the use of multigrid within shift-and-invert type eigensolvers. We show numerical results from our MPI-C implementation of a Rayleigh quotient iteration with multigrid. For state-of-the-art lat…
CCDC 916055: Experimental Crystal Structure Determination
2013
Related Article: Veronika Ehmke, Edwin Winkler, David W. Banner, Wolfgang Haap, W. Bernd Schweizer, Matthias Rottmann, Marcel Kaiser, Céline Freymond, Tanja Schirmeister, François Diederich|2013|ChemMedChem|8|967|doi:10.1002/cmdc.201300112
CCDC 916056: Experimental Crystal Structure Determination
2013
Related Article: Veronika Ehmke, Edwin Winkler, David W. Banner, Wolfgang Haap, W. Bernd Schweizer, Matthias Rottmann, Marcel Kaiser, Céline Freymond, Tanja Schirmeister, François Diederich|2013|ChemMedChem|8|967|doi:10.1002/cmdc.201300112