engleski

Small Molecule NMR: From Mixtures to Interactions

One and two-dimensional NMR techniques have experienced a rapid growth and widespread applications in drug research and development. Small organic molecules are still by far the most used drug molecules today. In this talk examples will be shown demonstrating the power of NMR to provide useful information on small bioactive compounds. To identify and structurally characterize small molecule impurities in drugs has become one of the primary goals of analytical chemists in modern pharmaceutical research. Interfacing liquid chromatography with NMR spectroscopy and/or mass spectrometry might provide a sophisticated and powerful approach to solve problems involving purity issues, degradation products or metabolism. The advantages and disadvantages of LC-NMR in analysis of drug impurities will be discussed. Furthermore, NMR spectroscopy has also proven usefull for identification and conformational analysis of small ligand molecules and structure-based inhibitor design. Many approaches have been developed to screen for small molecule binders and to establish structure activity relationships. An approach which combine NMR parameters such as spin-spin coupling constants, nOe and relaxation times coupled with molecular modelling was developed to study free conformations of macrolide antibiotics. Furthermore, an application of transferred nOe and STD NMR experiments provided information on the interactions and binding epitopes of macrolides and their target ribosome. The knowledge gained from such studies can help in developing strategies aiming at design of molecules with improved biological profile

NMR techniques; LC-NMR; macrolides; ribosomes; epitopes; drug design

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