Deuteration of Amino Acids Based on DCL™
Introduction to Amino Acids
As the basic unit of protein, amino acids are widely used in food, medicine, additives and cosmetics industries. As the bioengineering technology industry gradually becomes one of the major industries in the world in the 21st century, the demand for amino acids and the quality requirements are getting higher and higher. Amino acids are the raw materials for the synthesis of human proteins, hormones, enzymes and antibodies, and participate in normal metabolism and physiological activities in the human body. Based on the above properties, amino acids and their derivatives can be used as raw materials or additives for the development of biological drugs for the treatment of various diseases.
Deuterium-labeled compounds have been the focus of medicinal chemistry researchers since the first FDA-approved deuterated drugs for the treatment of chorea-associated Huntington's disease. Stronger C-D bonds reduce metabolism, provide higher dose potency and fewer side effects than C-H bonds. This indicates that the incorporation of deuterium exhibits important pharmacological properties that can improve the absorption, distribution, metabolism and excretion of drug candidates. Therefore, deuterium technology was developed to meet the urgent need for complex site-selective organic frameworks. The introduction of deuterium into amino acids can reduce the rate of epimerization, thereby increasing efficacy. In addition, deuterated amino acids are also very useful for elucidating the biosynthetic pathways, enzymatic mechanisms and structures of peptides/proteins.
Fig.1 Deuteration of amino acids at supercritical temperatures.[2]
NMR Study of Large Proteins Based on Deuterated Amino Acids
Many advances in protein NMR spectroscopy can be traced directly to the development of isotopic labeling strategies. While perdeuterated, selectively deuterated amino acids are powerful strategies to study the structure and dynamics of high molecular weight proteins, membrane proteins, and protein-protein complexes. For example, applications of ultra-high molecular weight complexes benefit significantly from the preparation of highly deuterated molecules, where the relaxation times of the remaining NMR probes (usually the backbone amide moiety or the side chain methyl groups) are significantly increased. This illustrates that the manner of deuterium labelling allows recording of spectra with higher sensitivity and resolution.
DCL™ in Deuterated Amino Acids
Our DCL™ technology platform enables the preparation of deuterium-labeled amino acids such as alanine, isoleucine, leucine, valine, methionine, glutamic acid, histidine, phenylalanine, tryptophan and tyrosine, etc. We avoided the use of expensive or sensitive catalysts and were able to obtain the corresponding deuterated products in a simplified process. Based on a "tailor-made" reaction system, we can easily achieve high levels of deuterium incorporation. It is believed that our DCL™ technology platform will be a powerful tool for the synthesis of new chemical entities.
References
- Li Liu, et al. Access to Deuterated Unnatural α-Amino Acids and Peptides by Photochemical Acyl Radical Addition. Org. Lett. 2021, 23, 14, 5299-530.
- Gaurav Prakash, et al. C–H deuteration of organic compounds and potential drug candidates. Chemical Society Reviews. 2022.
- Velyvis A, et al. An economical method for production of 2H, 13CH3-threonine for solution NMR studies of large protein complexes: application to the 670 kDa proteasome. 2012.
Customer Intellectual Property Protection
BOC Sciences has always regarded intellectual property as the most valuable asset of the company and its customers. We have signed non-disclosure agreements with customers and employees before the project starts, and provide synthetic route design and synthesis services in strict accordance with the terms of the non-disclosure agreement, striving to provide customers with target compounds in the shortest time possible.
