Alexander Bujotzek

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Multivalent ligand-receptor systems often show an enhancement in binding compared to the constituent monovalent systems. This "cooperativity effect" is often attributed to the favorable spatial preorganisation of the ligands by the connecting spacer that leads to a reduction of entropy loss at ligand binding. A different factor that has been proposed to(More)
Estrogen receptors are known drug targets that have been linked to several kinds of cancer. The structure of the estrogen receptor ligand binding domain is available and reveals a homodimeric layout. In order to improve the binding affinity of known estrogen receptor inhibitors, bivalent compounds have been developed that consist of two individual ligands(More)
The assembly of DNA complexes proceeds according to known rules. Thus, the mutual recognition of DNA conjugates can be used for the precise positioning of functional groups. For example, chromophores, metals, catalytic units, nanoparticles, fluorophores and even proteins have been arranged at well-defined distances by means of DNA hybridization. Until(More)
The understanding of biological ligand-receptor binding processes is relevant for a variety of research topics and assists the rational design of novel drug molecules. Computer simulation can help to advance this understanding, but, due to the high dimensionality of according systems, suffers from the severe computational cost. Based on the framework(More)
The estrogen receptor binding affinities of bivalent raloxifene ligands tethered by flexible spacers of different lengths have been evaluated in vitro. Two bivalent binding modes, intra- and intermolecular, were hypothesized to explain their different binding properties. The binding affinities of these bivalent ligands in an aqueous environment are(More)
The estrogen receptor (ER) is a hormone-regulated transcription factor that binds, as a dimer, to estrogens and to specific DNA sequences. To explore at a fundamental level the geometric and topological features of bivalent-ligand binding to the ER dimer, dimeric ER crystal structures were used to rationally design nonsteroidal bivalent estrogen ligands.(More)
Three polymers, poly(N-(2-hydroxypropyl)methacrylamide) (pHPMA), hyperbranched polyglycerol (hPG), and dextran were investigated as carriers for multivalent ligands targeting the adaptive tandem WW-domain of formin-binding protein (FBP21). Polymer carriers were conjugated with 3-9 copies of the proline-rich decapeptide GPPPRGPPPR-NH2 (P1). Binding of the(More)
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