Protein/ Peptide modification are often made by chemists to optimize lead peptide structures so as to achieve better activity and potency, making them more ideal for the target of interest. Scientists have discovered a new type of chemical modification that affects the function of multiple proteins in mammalian cells. This modification can regulate many important cellular processes in the cell, such as glucose metabolism processes. Further research on this protein modification can be important for a better understanding of diabetes, cancer and other types of diseases. The study was completed by the scientists from Scripps Research Institute (TSRI) and relevant reseach findings were published in the August 2 issue of Science.

Looking for new ways to modify proteins

Dr. Cravatt's lab has been working to study the effects of natural chemical modifications on protein function. The purpose is to learn more about protein modifications such as phosphorylation, acetylation, and more.

Dr. Cravatt and postdoctoral researcher Dr. Moellering are devoted to exploring the effects of 1,3-diphosphoglycerate (1,3-BPG) on proteins. 1,3-BPG is an important intermediate in the glycolysis process. The protein can be easily bound to other proteins after binding to 1,3-BPG.

Dr. Moellering began using test tube experiments to show that 1,3-BPG reacts with lysine to modify GAPDH, while GAPDH is an enzyme that produces 1,3-BPG. Dr. Moellering said that the experiment showed for the first time that the reaction did occur, so they started to study at the cellular level.

Its role in glucose metabolism

Dr. Moellering invented a new method to detect this lysine modified form in cultured human cells. He also found that the protein modification not only affects enzymes involved in glucose metabolism, but also affects enzymes not associated with glucose. Moreover, the protein modification pattern not only occurs in the cytoplasm but also affects the nucleus and plasma membrane associated proteins.

Dr. Moellering found that lysine modification of 1,3-BPG affects glucose-related enzymes, which inhibit the activity of these enzymes and slow down the metabolic process of glucose. As revealed by Dr. Moellering, the modification of 1,3-BPG seems to be sort of ancient negative feedback mechanism which can be used to regulate the main energy metabolism process of cells.

Looking to the future

Glucose metabolism abnormalities occur in many diseases including cancer and diabetes. Dr. Moellering said that cancer cells are found to consume 20 times more glucose than normal cells. Therefore, he believes that 1,3-BPG may be the key to abnormal glucose metabolism in cancer cells.

At the same time, Dr. Cravatt and Moellering also intend to further study the role of 1,3-BPG lysine modification in the nucleus and plasma membrane. They highly suspect that this modification may be linked to other pathways and glucose metabolism pathways, or perhaps some new signal path.

Post-translational Modification of proteins

Post-translational modification (PTM) refers to the covalent modification and enzymatic modification of a protein after biosynthesis. The modification can occur in the amino acid side chain and its C or N terminus. More function are introduced through modification of functional groups or introduction of new groups (such as phosphates, acetyl groups, etc.). Most proteins expressed by eukaryotes undergo a series of post-translational processing and modification to become the final complex function performer, so post-translational modification of proteins becomes an important aspect of proteomics research.

Because of the low content and wide dynamic range of post-transnationally modified proteins in the sample, the related research is very challenging. The combination of affinity enrichment, multi-dimensional separation and bio-mass spectrometry provides an opportunity for the development of post-translational modified proteomics. At present, protein modifications that have been subjected to scale studies mainly include phosphorylation, acetylation, glycosylation, and ubiquitination.

Post-translational modification is closely related to human health. Once the mechanism of disease occurrence is clearly defined, the technique of modifying histone code can be used to design drugs and propose measures to change or adjust the state and activity of gene expression. This can solve many diseases that cannot be cured by traditional drug therapy and gene therapy. For example, HDAC inhibitors have been studied in cancer, nerves, and circulatory diseases, and some drugs have been clinically tested.

Author's Bio: 

This article is written by scientists from Creative Peptides, a company specialized in peptide related custom services such as Amino Acids Modification, Peptide PEGylation, Post-translational Modification, Cyclic Peptide synthesis, Peptide Design, Recombinant Peptide Synthesis, etc.