In recent years, the developed residual dipole coupling (RDC) is anuclear magnetic resonance (NMR) parameter with more spatial structureinformation, which can construct the global stereoscopic structure of moleculesand push the molecular structure analysis more accurately to three-dimensionalspace. In particular, it can reflect the exact conformational information whichis difficult to obtain by both crystal diffraction (X-Ray) and electronmicroscopy (EM). However, the application of RDC has been severely restrictedfor a long time due to the lack of effective directional media and difficultyof detection, especially in organic solvents. Inspired by the aggregationeffect of Alzheimer's disease-related amyloid β-protein ( Aβ) ,theresearch group led by Professor Lei Xinxiang, School of Pharmacy of ouruniversity, used the aggregation function of the polypeptide KVLFF of its corefragment, of which the derivatization has obtained AAKLVFF polypeptide can begenerated with lyotropic liquid crystal, applicable to the determination ofnuclear magnetic resonance (NMR) residual dipolar coupling of natural product.The related work was recently published in the well-known international journalAngewandteChemie International Edition (Influence Factor: 11.99, Angew. Chem.Int. Ed. 2017, DOI: 10.1002/anie.201705123), and filed for patent protection.2016 graduate student Qiu Feng, 2014 undergraduate student Bai Liwen and Dr.Wang Wenxuan participated in the related study project.
This medium is the first directional liquid crystal of methanolsystem. It is demonstrated by taking artemisinin (artemether), plant hormonegibberellin (GA3), anti-tumor drug ginkgolide B, ingenol, actinomycin D and soon molecules as examples to validate its accuracy and reliability inmeasurement of RDC. It has the following characteristics: 1 It has a low (0.5%)critical concentration, low viscosity, good fluidity, easy shimming andcontrollable orientation angle in liquid crystal formation; 2 Self-assembly ofpolypeptides reduces the background signals. 3 It can be simply prepared andkept steadily for a long time. 4 It can be produced in large quantities and atlow price. This provides an easy way for non-nuclear magnetic resonanceprofessionals to use conventional RDC techniques to determine the molecularstructure of complex natural drugs.
The above-mentioned project has been supported by the NationalNatural Science Foundation and the International Cooperation Project ofSino-German Center (Grant No.: 21572164 and GZ1289).
Paper Catalogue Figures
Structure charts of polypeptide molecule and molecule to bedetected
Isotropic and anisotropic local two-dimensional maps of artemetherdrugs
Professor Lei Xinxiang's research group has long been engaged instudying the structural analysis of organic chemistry and natural drugs by NMRmethod. The research results on the new RDC method have been published in Chem.Eur.J. (2017, 23, 7653 – 7656), Magn. Reson. Chem. (2017, 55, 297- 303), Angew.Chem.Int.Ed. （2016,55,3690-3693,J. Am. Chem. Soc.(2014,136: 11280-11283), and hewas invited by the Chinese Journal ofScience China Chemistry to compose monograph review (under review). Atpresent, the research group is continuing to improve, expand and enrich the newmethods and applications of RDC in the determination of natural drugs andorganic molecules, and putting forth effort to build a drug screening andanalysis platform based on nuclear magnetic resonance technology and guided bytarget proteins in order to carry out application studies on screening,optimizing and mining over active ingredients of natural drugs.