A5065509900- Chemical Synthesis and Analysis
- Photochromic and Fluorescence Chemistry
- Photoreceptor and optogenetics research
- Protein Structure and Dynamics
- Click Chemistry and Applications
- Collagen: Extraction and Characterization
- Traditional and Medicinal Uses of Annonaceae
- Spectroscopy and Quantum Chemical Studies
- Cell Adhesion Molecules Research
- Mass Spectrometry Techniques and Applications
- Ubiquitin and proteasome pathways
- Lipid Membrane Structure and Behavior
- Enzyme Structure and Function
- Peptidase Inhibition and Analysis
- Health and Medical Studies
- Carbohydrate Chemistry and Synthesis
- Glycosylation and Glycoproteins Research
- Molecular spectroscopy and chirality
- Fluorine in Organic Chemistry
- Trace Elements in Health
- Cancer-related Molecular Pathways
- Supramolecular Self-Assembly in Materials
- Prion Diseases and Protein Misfolding
- Protein Hydrolysis and Bioactive Peptides
- Natural product bioactivities and synthesis
University of Kentucky
2025
Deggendorf Institute of Technology
2023
Arthrex (Germany)
2015-2022
Deutsche Forschungsgemeinschaft
2006-2020
Klinik und Poliklinik für Kinder- und Jugendmedizin
2018
München Klinik
2016
University of Stuttgart
2016
Helios Dr. Horst Schmidt Kliniken Wiesbaden
2012
Max Planck Institute of Biochemistry
2000-2010
Klinikum Aschaffenburg
2010
The oncoprotein MDM2 inhibits the tumor suppressor protein p53 by binding to transactivation domain. gene is inactivated in many human tumors either mutations or oncogenic proteins. In some tumors, such as soft tissue sarcomas, overexpression of inactivates an otherwise intact p53, disabling genome integrity checkpoint and allowing cell cycle progression defective cells. Disruption MDM2/p53 interaction leads increased levels restored transcriptional activity, indicating restoration check...
Femtosecond time-resolved spectroscopy on model peptides with built-in light switches combined computer simulation of light-triggered motions offers an attractive integrated approach toward the understanding peptide conformational dynamics. It was applied to monitor light-induced relaxation dynamics occurring subnanosecond time scales in a that backbone-cyclized azobenzene derivative as optical switch and spectroscopic probe. The femtosecond spectra permit clear distinguishing...
The preference of the peptidyl-fluoroproline amide bond for cis or trans conformation in model compounds N-acetyl-4-fluoroproline methyl esters fully correlates with thermostability related mutants protein barstar. Thus, (4S)-L-FPro show a higher and the(4R)-L-FPro lower thermal stability than
The technique of transient two-dimensional infrared (T2D-IR) spectroscopy is introduced, which extends the advantage 2D-IR to investigation a species with picosecond time resolution. conformational change small cyclic peptide studied in amide-I spectral range, induced by means photoswitch integrated into backbone. Substantial changes are found spectra at times when 1D show only minor dependence, illustrating information gain accessible from spectroscopy. In contrast spectroscopy, can...
Ultrafast IR spectroscopy is used to monitor the nonequilibrium backbone dynamics of a cyclic peptide in amide I vibrational range with picosecond time resolution. A conformational change induced by means photoswitch integrated into backbone. Although main completed after only 20 ps, subsequent equilibration new region space continues for times >16 ns. Relaxation and processes occur on discrete hierarchy scales. Albeit possessing few degrees freedom compared protein, behaves highly...
The cisright harpoon over left trans photoisomerization of the azobenzene building block 4-(4-aminophenylazo)benzoic acid incorporated in a cyclic peptide (see scheme) facilitated two-state transition chain from rigid constrained conformation isomer into largely free conformational space cis isomer.
Dihydrodipicolinate synthase (DHDPS) catalyzes the condensation of pyruvate with L-aspartate beta-semialdehyde. It is first enzyme unique to diaminopimelate pathway lysine biosynthesis. Here we present crystal structures five complexes Escherichia coli DHDPS substrates, substrate analogs, and inhibitors. These include (1) pyruvate, (2) beta-semialdehyde analog succinate beta-semialdehyde, (3) inhibitor alpha-ketopimelic acid, (4) dipicolinic (5) natural feedback L-lysine. The kinetics...
The reversible, optical switching of individual polymer molecules was observed using molecular force spectroscopy. We synthesized a polypeptide with multiple photoactive azobenzene groups incorporated in the backbone. contour length could be selectively lengthened or shortened by between trans- and cis-azo configurations 420 365 nm wavelength light, respectively. This cis- to trans-azo configurational transition induced ultraviolet light resulted measurable change length. at low under...
At the flick of a switch: Two side chains collagen peptide containing (2S,4S)-mercaptoproline at two defined positions are linked with diiodo azobenzene derivative. With trans isomer clamp (orange), folds into triple helix (green, blue, gray), which unfolds upon irradiation 330 nm. The light-controlled folding/unfolding processes fully reversible, making this system well-suited for ultrafast spectroscopic analysis. Supporting information article is available on WWW under...
Free radical polymerization of methacrylamide-based bisphosphonates turns weak arginine binders into powerful polymeric protein receptors. Dansyl-labeled homo- and copolymers with excellent water solubility are accessible through a simple copolymerization protocol. Modeling studies point to striking structural difference between the stiff rodlike densely packed homopolymer 1 flexible copolymer 2 spatially separated bisphosphonate units. Fluorescence titrations in buffered aqueous solution...
Beta-hairpins constitute the smallest beta-type structures in peptides and proteins. The development of highly stable, yet monomeric beta-hairpins based on tryptophan zipper motif was therefore a remarkable success [A. G. Cochran, N. J. Skelton, M. A. Starovasnik, Proc. Natl. Acad. Sci USA 2001, 98, 5578-5583]. We have been able to design, synthesize characterize hairpin this which incorporates an azobenzene-based photoswitch, that allows for time-resolved folding studies beta-structures...
Azobenzene is a common light switch. Azobenzene, as ω-amino acid derivative in peptides, exhibits redox properties that make it susceptible to reduction by thiols with concurrent thiol-induced enhanced thermal Z-to-E isomerization rates. Supporting information for this article available on the WWW under http://www.wiley-vch.de/contents/jc_2268/2007/z600495_s.pdf or from author. Please note: The publisher not responsible content functionality of any supporting supplied authors. Any queries...
A light-switchable peptide is transformed with ultrashort pulses from a β-hairpin to an unfolded hydrophobic cluster and vice versa. The structural changes are monitored by mid-IR probing. Instantaneous normal mode analysis Hamiltonian combining density functional theory molecular mechanics used interpret the absorption transients. Illumination of state triggers unfolding reaction that visits several intermediates reaches within few nanoseconds. In this equilibrium conformation, system does...
Based on information from the X-ray structure of TMC-95A/proteasome complex, TMC-95A (A) was reduced to minimum core (B). The inhibitory potency synthetic analogue confirms that simplified ring may well serve as lead for further improvement affinity and selectivity reversible proteasome inhibitors. is an intracellular multicatalytic protease complex which in combination with ubiquitin pathway plays a central role major cellular processes, such antigen presentation, cell proliferation...
Spot the difference: Conformational analysis of 2S,4R and 2S,4S epimers N-acetyl-4-mercaptopyrrolidine-2-carboxylic acid methyl esters reveals ring-pucker preferences that are opposite those hydroxyproline derivatives (see scheme). Replacement proline or in polypeptides with chalcogen analogue should allow for fine-tuning complex interplay noncovalent interactions, steric hindrance, stereoelectronic effects. Supporting information this article is available on WWW under...