Proteins are often used in medicine to deliver drugs to the body and maintain the activity of these drugs in the body. Fundamental research has now provided a better understanding of the body’s own processes. As well as a significant boost to the manufacture of improved protein therapeutics.
Lipids are inserted into proteins as carriers for drugs during the preparation of these proteins. Lipids is a collective term for completely – or at least largely – water-insoluble natural substances. However, due to their low polarity, they can be dissolved very well in hydrophobic ( also known as lipophilic ) solutions such as hexane.
The body’s own processes
Protein therapeutics refer to the body’s own processes. A protein is a biological macromolecule composed of amino acids and peptide bonds. Some proteins are also made up of fat-like lipid chains which in turn have a decisive influence on the biological properties of the protein. For example, the Ras protein is responsible for the development of numerous types of cancer. However, it only becomes active and carcinogenic if it is able to bind to a membrane via a fat that is anchored to it.
Palladium as a catalyst
Current methods for inserting lipids into proteins, however, are costly and time-consuming. Rolf Breinbauer from the Institute of Organic Chemistry at the the Graz Technical University and Christian Becker from the Department of Biological Chemistry at the University of Vienna, have now developed a much simpler and more direct method. They found a catalyst in the precious metal palladium which makes it possible to attach lipids to proteins. A catalyst refers to a chemical substance. This accelerates the reaction speed of a chemical reaction by lowering its activation energy, although it is not used in the process itself.
Coordinated bond
The BiPhePhos ligand plays a decisive role in this newly discovered process. A ligand is an atom or molecule that binds to a central metal atom to form a coordinate bond, also called a dative covalent bond. The researchers tested a total of fifty different ligands. Yet only BiPhePhos has the specific selectivity required for palladium to enable lipidation of the sulfur-containing amino acid cysteine.
Rapid modification
Protein chemist Christian Becker applied these results to proteins. His experiments were also successful. The researcher highlighted the excellent selectivity of the new catalyst and its robust reaction. These properties enable the rapid modification of a large number of cysteine-containing peptides and proteins for biomedical research.
The reagents that are used are very easy to manufacture or can be purchased commercially. The researchers are confident that this method for the faster and easier manufacture of protein therapeutics will soon come into practice.
The research project was funded as a stand-alone project by the FWF Austrian Science Fund (FWF).
The study was presented in the Journal of the American Chemical Society (JACS). You can find the link here.
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