Stefan Wetzel

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A hierarchical classification of chemical scaffolds (molecular framework, which is obtained by pruning all terminal side chains) has been introduced. The molecular frameworks form the leaf nodes in the hierarchy trees. By an iterative removal of rings, scaffolds forming the higher levels in the hierarchy tree are obtained. Prioritization rules ensure that(More)
Natural products are a heterogeneous group of compounds with diverse, yet particular molecular properties compared to synthetic compounds and drugs. All relevant analyses show that natural products indeed occupy parts of chemical space not explored by available screening collections while at the same time largely adhering to the rule-of-five. This renders(More)
We describe Scaffold Hunter, a highly interactive computer-based tool for navigation in chemical space that fosters intuitive recognition of complex structural relationships associated with bioactivity. The program reads compound structures and bioactivity data, generates compound scaffolds, correlates them in a hierarchical tree-like arrangement, and(More)
Cycles of depalmitoylation and repalmitoylation critically control the steady-state localization and function of various peripheral membrane proteins, such as Ras proto-oncogene products. Interference with acylation using small molecules is a strategy to modulate cellular localization--and thereby unregulated signaling--caused by palmitoylated Ras proteins.(More)
The identification of small molecules that fall within the biologically relevant subfraction of vast chemical space is of utmost importance to chemical biology and medicinal chemistry research. The prerequirement of biological relevance to be met by such molecules is fulfilled by natural product-derived compound collections. We report a structural(More)
Biologically active small molecules represent the basis for chemical biology applications in which small molecules are used as chemical tools to probe biological processes. In this report, we review two approaches to design and synthesize compound libraries for biological screenings, i.e., diversity-oriented synthesis (DOS) and biology-oriented synthesis(More)
D-Alanine-D-alanine ligase (DDl) is an essential enzyme in bacterial cell wall biosynthesis and an important target for developing new antibiotics. Here, we describe a new approach to identify new inhibitor scaffolds for DDl based on similarity in the ATP binding region of different kinases and DDl. After an initial screening of several protein kinase(More)
A matter of common sense: a common recognition motif consisting of a negatively charged group five to six bonds away (red) from the (thio)ester functionality (green) and a positively charged tail group ten to twelve bonds away (blue) was identified in two native acyl protein thioesterase 1 (APT1) substrates. This similarity led to the design of potent(More)
Post-translational modifications of histones by chromatin modifying enzymes regulate chromatin structure and gene expression. As deregulation of histone modifications contributes to cancer progression, inhibition of chromatin modifying enzymes such as histone demethylases is an attractive therapeutic strategy to impair cancer growth. Lysine-specific(More)
Post-translational attachment of geranylgeranyl isoprenoids to Rab GTPases, the key organizers of intracellular vesicular transport, is essential for their function. Rab geranylgeranyl transferase (RabGGTase) is responsible for prenylation of Rab proteins. Recently, RabGGTase inhibitors have been proposed to be potential therapeutics for treatment of cancer(More)