Researchers at the RUB and from Berkeley have used metal complexes to modify peptide hormones. In the Journal of the American Chemical Society, they report for the first time on the three-dimensional structure of the resulting metal-peptide compounds.
“With this work, we have laid the molecular foundation for the development of better medicines” says Prof. Raphael Stoll from the Faculty of Chemistry and Biochemistry at the Ruhr-University. The team examined hormones that influence the sensation of pain and tumour growth.
Peptide hormones have many functions in the body
Hormones consisting of amino acids, the peptide hormones, convey bodily sensations such as pain and hunger, but also transmit growth signals. One example of this is insulin, which is important for the control of blood sugar levels. In interaction with specific receptors, the G-protein-coupled receptors, peptide hormones transport their messages to the cells. The hormones can be specifically chemically modified so that their effect changes, for example pain tolerance is lowered, or tumour growth inhibited. The German-Californian group of researchers has now found a new way to modify peptide hormones.
Metal complexes react with various peptide hormones
The first time they used a metal complex, namely, a rhodium compound, which reacts with the amino acid tyrosine. The precious metal rhodium is used as a catalyst in the synthesis of highly complex medicinal substances in the research laboratory as well as in industrial plants. Among other things, the researchers analysed the peptide hormone encephalin, which is important for the sensation of pain, and octreotide. The latter is a synthetic derivative of the growth hormone somatostatin, approved as a medicinal substance and already used in the treatment of certain tumours. The reaction with the metal complex was highly selective. Although the hormones consist of hundreds of atoms, the rhodium compound was always coordinated by the carbon ring of the tyrosine - the phenol ring.
Structure determined by NMR spectroscopy
The team also clarified the structure of the resulting metal-peptide complexes. “We hope to develop other metal-containing, peptide-like substances by building on these basic studies” says Prof. Dr. Nils-Metzler-Nolte of the Chair of Inorganic Chemistry I. “These could modulate the effect of naturally occurring peptide hormones and, for example, be used as a novel remedy for pain or cancer”. For the project, the Californian colleagues made their knowledge of the special reactivity of the rhodium compound available. The researchers in Bochum contributed their experience with metal-peptides, the corresponding receptors and the structural analysis of biological macromolecules. “This again demonstrates that cutting-edge competitive research can only be carried out efficiently within a research association”, says Prof. Stoll. The German Research Foundation (SFB 642 and Research Unit 630) and the Research Department for Interfacial Systems Chemistry at RUB supported the work.
Bibliographic recordH. Bauke Albada, F. Wieberneit, I. Dijkgraaf, J.H. Harvey, J.L. Whistler, R. Stoll, N. Metzler-Nolte, R.H. Fish (2012): The chemoselective reactions of tyrosine-containing G-protein-coupled receptor peptides with [Cp*Rh(H2O)3](OTf)2, including 2D NMR structures and the biological consequences, Journal of the American Chemical Society, doi: 10.1021/ja303010k
Further informationProf. Dr. Nils Metzler-Nolte, Inorganic Chemistry I, Faculty of Chemistry and Biochemistry at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-24153
firstname.lastname@example.orgProf. Dr. Raphael Stoll, Biomolecular Spectroscopy, Faculty of Chemistry and Biochemistry at the Ruhr-Universität, 44780 Bochum, Germany, Tel. +49/234/32-25466
Click for moreMedical inorganic chemistry at the RUB
Dr. Josef König | idw
Barium ruthenate: A high-yield, easy-to-handle perovskite catalyst for the oxidation of sulfides
16.07.2018 | Tokyo Institute of Technology
The secret sulfate code that lets the bad Tau in
16.07.2018 | American Society for Biochemistry and Molecular Biology
For the first time ever, scientists have determined the cosmic origin of highest-energy neutrinos. A research group led by IceCube scientist Elisa Resconi, spokesperson of the Collaborative Research Center SFB1258 at the Technical University of Munich (TUM), provides an important piece of evidence that the particles detected by the IceCube neutrino telescope at the South Pole originate from a galaxy four billion light-years away from Earth.
To rule out other origins with certainty, the team led by neutrino physicist Elisa Resconi from the Technical University of Munich and multi-wavelength...
For the first time a team of researchers have discovered two different phases of magnetic skyrmions in a single material. Physicists of the Technical Universities of Munich and Dresden and the University of Cologne can now better study and understand the properties of these magnetic structures, which are important for both basic research and applications.
Whirlpools are an everyday experience in a bath tub: When the water is drained a circular vortex is formed. Typically, such whirls are rather stable. Similar...
Physicists working with Roland Wester at the University of Innsbruck have investigated if and how chemical reactions can be influenced by targeted vibrational excitation of the reactants. They were able to demonstrate that excitation with a laser beam does not affect the efficiency of a chemical exchange reaction and that the excited molecular group acts only as a spectator in the reaction.
A frequently used reaction in organic chemistry is nucleophilic substitution. It plays, for example, an important role in in the synthesis of new chemical...
Optical spectroscopy allows investigating the energy structure and dynamic properties of complex quantum systems. Researchers from the University of Würzburg present two new approaches of coherent two-dimensional spectroscopy.
"Put an excitation into the system and observe how it evolves." According to physicist Professor Tobias Brixner, this is the credo of optical spectroscopy....
Ultra-short, high-intensity X-ray flashes open the door to the foundations of chemical reactions. Free-electron lasers generate these kinds of pulses, but there is a catch: the pulses vary in duration and energy. An international research team has now presented a solution: Using a ring of 16 detectors and a circularly polarized laser beam, they can determine both factors with attosecond accuracy.
Free-electron lasers (FELs) generate extremely short and intense X-ray flashes. Researchers can use these flashes to resolve structures with diameters on the...
13.07.2018 | Event News
12.07.2018 | Event News
03.07.2018 | Event News
16.07.2018 | Physics and Astronomy
16.07.2018 | Life Sciences
16.07.2018 | Earth Sciences