A5081381092- Chemical Synthesis and Analysis
- Cell Adhesion Molecules Research
- Molecular spectroscopy and chirality
- Carbohydrate Chemistry and Synthesis
- Advanced NMR Techniques and Applications
- Monoclonal and Polyclonal Antibodies Research
- Protein Structure and Dynamics
- Glycosylation and Glycoproteins Research
- Peptidase Inhibition and Analysis
- Analytical Chemistry and Chromatography
- NMR spectroscopy and applications
- Click Chemistry and Applications
- DNA and Nucleic Acid Chemistry
- Protease and Inhibitor Mechanisms
- Cellular Mechanics and Interactions
- Biochemical and Structural Characterization
- Electron Spin Resonance Studies
- Inorganic and Organometallic Chemistry
- Neuropeptides and Animal Physiology
- Enzyme Structure and Function
- RNA and protein synthesis mechanisms
- Mass Spectrometry Techniques and Applications
- Asymmetric Synthesis and Catalysis
- Receptor Mechanisms and Signaling
- Signaling Pathways in Disease
Technical University of Munich
2016-2025
Institute for Advanced Study
2016-2025
Center for Integrated Protein Science Munich
2013-2024
Chemie³ (Germany)
2021
Lawrence Livermore National Laboratory
2019
Laser Zentrum Hannover
2019
Pacific Northwest National Laboratory
2019
University of Central Florida
2019
University of New Mexico
2019
University of California, Davis
2018-2019
To study the function behind molecular arrangement of single integrins in cell adhesion, we designed a hexagonally close-packed rigid template cell-adhesive gold nanodots coated with cyclic RGDfK peptide by using block-copolymer micelle nanolithography. The diameter adhesive dots is < 8 nm, which allows binding one integrin per dot. These are positioned high precision at 28, 58, 73, and 85 nm spacing interfaces. A separation > or = 73 between results limited attachment spreading,...
Abstract Cyclic peptides containing biologically active hormone sequences are suitable models for studying conformation‐activity relationships. In such the usual flexibility of peptide chains is reduced by their cyclic arrangement. However, conformational analysis systems experimental means possible only if a single conformer predominates at equilibrium, and criteria this put forward. NMR spectroscopic methods, including many recent advances, discussed in relation to ability contribute analysis.
The alpha(V)beta(3) integrin receptor plays an important role in human tumor metastasis and tumor-induced angiogenesis. vivo inhibition of this by antibodies or cyclic peptides containing the RGD sequence may future be used to selectively suppress these diseases. Here we investigate influence N-methylation active selective antagonist cyclo(RGDfV) (L1) on biological activity. Cyclo(RGDf-N(Me)V-) (P5) was found even more than L1 is one most compounds inhibiting vitronectin binding integrin....
The αVβ3 integrin is implicated in human tumor metastasis and angiogenesis. design of low-molecular-mass antagonists by "spatial screening" led to the highly active peptides c(RGDFV) c(RGDFV). Here influence amino acids positions 4 5 flanking RGD-sequence on inhibition vitronectin fibrinogen binding isolated αIIbβ3 receptors was investigated. side chain backbone conformation activity selectivity studied. compounds were divided into conformational classes. For each class at least one...
Abstract Rotations and inversions in organic molecules are readily recognizable from the temperature dependence of NMR spectra. The study effects substituents on activation barriers such processes permits elucidation reaction mechanisms, stability limits isomers can also be determined. knowledge is necessary for specific synthesis stable rotamers invertomers.
Cyclic Arg‐Gly‐Asp‐Phe‐Val peptides with either D‐Phe or D‐Val residues were 20‐ to more than 100‐fold better inhibitors of cell adhesion vitronectin and/or laminin fragment P1 when compared a linear variant Gly‐Arg‐Gly‐Asp‐Ser. No only little increase in inhibitory capacity was observed for fibronectin and the binding platelet receptor αIIbβ3 fibrinogen. NMR studies two most active cyclic showed both an all‐ trans conformation βII′ γ turn. Subtle conformational differences, however, exist...
The binding of purified fibrinogen receptor alpha IIb beta 3, vitronectin V and fibronectin 5 1 to their corresponding ligands in solid-phase assays was used examine the inhibitory activity various linear cyclic penta- hexapeptides different conformation containing RGD or RAD sequences. Cyclic peptides with defined backbone conformations were designed by introducing a single D-amino acid proline at positions ring. data calibrated for 3 integrin incorporated into planar lipid bilayer physical...
We herein present a novel platform of well-controlled ordered and disordered nanopatterns positioned with cyclic peptide arginine-glycine-aspartic acid (RGD) on bioinert poly(ethylene glycol) background, to study whether the nanoscopic order spatial patterning integrin-specific ligands influences osteoblast adhesion. This is first time that nanoscale RGD ligand patterns was varied quantitatively, tested for its impact adhesion tissue cells. Our findings reveal integrin clustering such...
The potential of peptides as drug candidates is limited by their poor pharmacokinetic properties. Many have a short half-life in vivo and lack oral availability. Inspired the excellent profile cyclosporine, natural, multiply N-methylated cyclic peptide, we envisioned multiple N-methylation promising way to rationally improve key characteristics. In this Account, summarize our efforts toward modulating properties N-methylation. As first step, simplified synthesis amino acids solution,...
Abstract Integrins, a diverse class of heterodimeric cell surface receptors, are key regulators structure and behaviour, affecting morphology, proliferation, survival differentiation. Consequently, mutations in specific integrins, or their deregulated expression, associated with variety diseases. In the last decades, many integrin-specific ligands have been developed used for modulation integrin function medical as well biophysical studies. The IC 50 -values reported these strongly vary...
Background The integrin αvβ3 plays an important role in angiogenesis and tumor cell metastasis, is currently being evaluated as a target for new therapeutic approaches. Several techniques are studied to enable noninvasive determination of expression. We developed [18F]Galacto-RGD, 18F-labeled glycosylated antagonist, allowing monitoring expression with positron emission tomography (PET). Methods Findings Here we show by quantitative analysis images resulting from small-animal PET scanner...
Abstract Rotations‐ und Inversionsprozesse in organischen Molekülen geben sich durch die Temperaturabhängigkeit der NMR‐Spektren zu erkennen. Das Studium Substituenteneffekte auf Aktivierungsbarrieren solcher Prozesse gestattet Aufklärung von Reaktionsmechanismen, ferner lassen Stabilitätsgrenzen Isomeren ermitteln. Die Kenntnis ist notwendig, um gezielt stabile Rotamere Invertomere synthetisieren können.
Abstract An exact knowledge of the structure, dynamics, and reactions molecules provides key to understand their functions properties. NMR spectroscopy has developed, through introduction two‐dimensional methods, into most important method for investigation these questions in solution. A great variety different techniques is available. However, successful application not only appropriate equipment required, but also right choice experiments optimum measurement parameters, as well a careful...
Abstract Cell–cell and cell–matrix interactions play a major role in biology. An important class of surface receptors are the integrins, which exist number subtypes involved many biological processes, for example embryonic development, blood coagulation, osteoporosis, cancer, regulation balance between proliferation death (apoptosis) cell. Therefore, selective inhibition specific integrin is great pharmaceutical interest. It possible to develop highly active inhibitors especially α v β 3...
Full methyl jacket? A complete library of the N-methylated somatostatin cyclopeptidic analogue Veber–Hirschmann peptide cyclo(-PFwKTF-) has been prepared with aim improving its bioavailability. Several analogues from were found to bind receptor in nanomolar range and one them shows a significant oral bioavailability 10 %. Conformational analysis that N-methylation is allowed at specific positions without affecting bioactive conformation. Supporting information for this article available on...