Developing the NMR method for drug structure elucidation

In the late 1950s and 1960s, more than 12,000 deformed babies with short arms and legs were born as a side effect of thalidomide, a drug sold to pregnant women to prevent morning sickness. The tragedy was caused by a side effect of the drug, which was present in a racemic mixture of two mirror image forms. Research to determine the molecular structure of various compounds is essential for understanding biological phenomena and developing drugs to treat diseases and is primarily based on the interpretation of frequency signals as measured by nuclear magnetic resonance (NMR) spectroscopy.

Drs. Jinwook Cha and Jinsoo Park of the Natural Product Informatics Research Center at the Korea Advanced Institute of Science and Technology (KIST) announced that they have developed the first NMR (Ultselective Heteronuclear Polarization Method, or UHPT) method that can selectively measure information from the nuclei of carbon atoms. related to the specific hydrogen in a single measurement.

Even with existing ultra-high-field NMR equipment costing 10 billion won, only selective NMR signal measurements of specific hydrogen nuclei are possible. However, rapid measurement of the carbon core signal is not possible, making it difficult to secure a satisfactory level of resolution of the specific hydrogen-carbon NMR signal. In addition, there are limitations in identifying the chemical structure of pharmaceutical raw materials and drugs that have toxicity problems.

With the UHPT method, the researchers were able to distinguish carbons associated with specific hydrogen nuclei in a single measurement among complex carbon-carbon NMR signals, with a signal resolution of a few hertz (Hz). The method allowed them to clearly analyze the structure of natural products with complex molecular structures, such as the anticancer drug dactinomycin, which is composed of optical isomers of amino acids. This also allows the accurate assignment of the fungicide iprovicarb, a mixture of diastereoisomers.

The UHPT method is fast, accurate, and economical compared to conventional methods. When applied to NMR equipment owned by universities and companies, it has been confirmed that equivalent NMR signal resolution can be achieved in about one-fifth the measurement time of very high-field NMR equipment.

“The new NMR method can be used as a standard analytical technique to identify and standardize the active ingredients of new materials in the natural bio product industry,” said Dr. Jin-Wook Cha from KIST. “It is hoped that this will contribute to the development of the natural product bioproduct industry by solving the challenges of the drug development process by using it to identify the structure of particulate particles, which play an important role in determining drug efficacy and safety. ”

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KIST was founded in 1966 as the first government-funded research institute in Korea. KIST now seeks to solve national and social challenges and secure engines of growth through leading and innovative research. For more information, please visit the KIST website at https://eng.kist.re.kr/

This research was supported by the Ministry of Science and ICT (Minister Lee Jong-ho) through the KIST Main Project and published on June 2 as a cover article in the latest issue of Angewandte Chemie International Edition (IF 16.82), an academic journal in chemistry.