||Yuichi Umegawa, Nobuaki Matsumori, Michio Murata, Annual Reports on NMR Spectroscopy Vol 94 Chapter 2, Academic Press, doi.org/10.1016/bs.arnmr.2017.12.003, Vol 94, Chapter 2 Chapter Two - Recent Solid-State NMR Studies of Hydrated Lipid Membranes, page 41-72, 2018.01, Interactional and structural analyses of lipids in hydrated biomembranes are at the frontier of membrane physics and biology. Recently, solid-state NMR has emerged as a frequently used technique for the investigation of biomembrane systems, leading to particularly remarkable advances in the study of the structural biology of membrane proteins. However, conformational and interactional analyses of lipid molecules and membrane-active small compounds remain challenging. This chapter highlights recent applications of solid-state NMR to membrane lipids and nonpeptidic molecules such as membrane-active natural products. Lipid rafts are microdomains in cellular membranes formed by sphingomyelin and cholesterol and are thought to constitute a platform for signal transduction. Amphotericin B, theonellamide-A, and amphidinol 3 exert their activities by interacting with lipid membranes. Deuterium quadrupole coupling combined with dipole–dipole interactions has been used to evaluate the interaction modes and dynamic properties of membrane lipids and small membrane-active compounds. Herein, we review the recent advances in these topics using our recent research studies as examples of solid-state NMR investigations of hydrated lipid bilayers..
||Nobuaki Matsumori, Michio Murata, Experimental Approaches of NMR Spectroscopy, Springer, Singapore, 383-414, 2018.03, In this chapter we overview two topics on NMR methodologies for small molecules, mostly natural products; one is about the solution NMR-based methods used for stereochemical determination of natural products, and the other is on the solid-state and other techniques for investigating natural product-membrane interactions. Since important two methods for stereochemical analysis of natural products, namely the J-based configuration analysis (JBCA) and universal NMR database (UDB) methods, were reported in the 1990s, both methods have been widely used in the field of natural products. The newly coming RDC method is not the major method in the field of natural products yet, but will surely be an important tool for the stereochemical correlation between distant stereogenic centers, which could provide invaluable information as to the whole shape of natural products in solution. In the latter part of this chapter, we discuss the application of solid-state and other NMR techniques to membrane interaction analysis of natural products. In particular, we describe three examples of natural products that interact with biological membranes such as amphotericin B, erythromycin A, and theonellamide A. As shown in NMR studies of amphotericin B, natural products often reveal very high affinities for phospholipids and sterols in bilayer membranes. Solid-state NMR, therefore, provides a very promising approach toward the structure study of membrane-active complexes formed by natural products that have high affinity to lipids. In addition, solution NMR techniques can be applied to elucidate the structural features of membrane-bound small molecules such as antibiotic erythromycin A and membrane-disrupting cyclic peptide theonellamide A. Standard 2D 1H–1H experiments such as COSY (correlation spectroscopy), NOESY (nuclear Overhauser effect spectroscopy), and DOSY (diffusion-ordered spectroscopy) are often helpful in elucidating the membrane interaction between natural products and lipids. .