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DNA quadruplex structures have been of considerable interest as supramolecular self-assembling systems [1] and because of their potential biological importance in the regulation of a variety of processes within the cell cycle including replication, transcription, and recombination [2]. The observation that the telomeric repeats at the ends of chromosomes (5′-TTAGGG in humans) are able to assemble in the presence of monovalent cations into folded structures containing stacked G-tetrads has bought them into focus as a drug target, notably to interfere with telomere maintenance in immortalized human tumorderived cell lines by inhibiting the enzyme telomerase [1-6]. The novel fluorinated polycyclic quinoacridinium cation RHPS4 (Figure la) shows enhanced binding to higher-ordered DNA structures (triplex/quadruplex) and is a potent inhibitor of telomerase function [7,8]. To investigate the drug-quadruplex interaction, as part of a rational ligand design approach, we have studied by NMR the structure (Figure lb) and dynamics of the RHPS4 complex with the intermolecular parallel-stranded quadruplex d(TTAGGGT)_4, formed from the human telomeric repeat [9,10].

While conventional bioassay-based high-throughput screening (HTS) remains a mainstream approach for lead discovery, its limitations have driven the development of alternative and complementary tools. In this regard, novel NMR-based approaches that have emerged over the last few years show great promise. We have used NMR-based screening approaches for a variety of drug targets to identify low molecular weight (MW) small molecule hits from customized libraries, which subsequently could be optimized into leads through focused, structure-guided chemistry. Focus was placed on targets for which HTS failed to identify suitable leads. This report discusses different NMR-based screening techniques and follow-up strategies for lead discovery and illustrates their application to the NS3 protease and NS3 helicase domains of the hepatitis C virus (HCV).

Structural genomics (or more correctly structural proteomics) involves the high-throughput determination of protein structures on a genome-wide scale. It is a new field of research that has the potential to add substantial value to the sequence information becoming available from genome projects. The purpose of structural genomics is to accelerate protein structure determination so as to obtain structural examples of all available protein folds. The derived information will be essential in providing new insights into relationships between protein sequence, structure, and function.

Owing to enormous industrial use, elastomers remain an important field of intensive NMR studies [1-15] since more than three decades. The major goal is to establish a correlation between the molecular structure, molecular dynamics and the macroscopic mechanical properties of final materials. On this basis, material properties can be tailored using an optimization of the technological procedures and an application of cross-linking agents and special additives [16,17].

Since their discovery in 1991 [1], carbon nanotubes (CNTs) have attracted much attention due to their unique mechanical and electronic properties. Single-walled carbon nanotubes (SWNTs) can be envisioned as a single sheet of graphite rolled into a seamless tube. In multiwalled carbon nanotubes (MWNTs), several of these tubes are stacked inside each other in a concentric fashion. The length and direction of the roll-up vector determine the diameter and chirality of the tube. Statistically, one-third of tubes should be metallic, while the other two-thirds are semi-conducting [2]. Potential applications of CNTs range from field-emitting devices to gas sensors [3].

The long-established method of distinguishing between heterogeneous and homogeneous line shapes was introduced in the seminal paper by Bloembergen et al. [1]. The differentiation between the two types of spectral lines is based on whether one can alter the shape or just the amplitude of a line by an external perturbation. This concept has been applied many times particularly in optical hole burning spectroscopy where the distribution of transition frequencies can often be traced back to structural inhomogeneities in the material under study. It is well known that the frequency of an electronic transition, for example, sensitively depends on the local symmetry. This technique has been successfully applied to the structural elucidation of glasses [2].

In the past, nuclear magnetic resonance (NMR) studies have proved useful for structural investigations of magnetic multilayers in the direct space and at the atomic scale, complementing standard structural investigations [1]. Actually NMR provides with an original insight into the structural and magnetic characterization of composite nanostructured materials. Indeed the yield of NMR experiments is twofold. On one hand, the NMR spectrum, usually acquired in zero external field, reflects the distribution of hyperfine fields in the sample, and thus gives information about the different chemical configurations and site symmetries in the sample, the different phases, their structure, and their defects. On the other hand, the evolution of the spectral shape against the external field strength and orientation or against the radio frequency field strength probes the magnetic anisotropy or the magnetic stiffness of the electronic moments around the nucleus site, thus providing an information comparable to that given by ferromagnetic resonance (FMR) measurements. Therefore, combining both yields makes it possible to correlate the inhomogeneous magnetic properties of a composite sample to its different structural components [2]. The structural aspects of NMR studies are summarized in the first part of the chapter. Most of the chapter is devoted, though, to the analysis of NMR data in terms of local magnetic properties.

Nuclear magnetic resonance (NMR) is an established powerful analytical tool widely used for structural and conformational analysis in chemistry, biology, medicine, and material science [1,2]. Material characterization is mainly carried out by measuring NMR parameters like the chemical shift, the nuclear spin relaxation times, the dipolar coupling, and the self-diffusion coefficient. Furthermore, NMR is employed to produce images contrasted by these parameters, and to characterize diffusive and coherent molecular motion in a non-invasive fashion. NMR methods have been initially developed to work in the homogeneous fields of strong magnets, but the limited working volume of these devices restricts the applications of NMR, in particular for in situ studies of large objects. But in addition to conventional NMR, where the sample is adapted to fit into the probe, there is insideout NMR, which uses open magnet geometries specially adapted to the object under study. Such open magnets can be inexpensive and portable. They provide excellent versatility in accessing a large number of applications by NMR, which are inaccessible to closed magnet geometries. Historically the inside-out concept was developed for examining geological formations by lowering a full NMR spectrometer into a borehole to record signals from different formations [3]. Different tool geometries have been designed for well-logging [3,4] and water reservoir studies [5]. Later on the concept of single-sided NMR was extended to moisture detection in composites [6], medical diagnostics [7,8], and material analysis and quality control [9,10]

Xerogels, aerogels and other nanoporous solids are an important class of materials in electrochemical and catalytic process design. The preparation of these materials by sol-gel processing has become an important field in materials science [1]. In hydrolytic processes, the texture and structure of sol-gel-based materials largely depend on synthetic parameters, such as (i) solvent, (ii) temperature, (iii) monomer to water ratio, etc. Considerable work has been done to identify the relevant synthetic parameters in order to control the surface and porosity of xerogels (and aerogels). NMR spectroscopy has been extensively used to investigate the effect of these parameters in the sols, prior to gelation, or in the xerogels, after aging and drying [2-5].

Carrageenan is the generic name for a family of linear, sulphated galactans, obtained by extraction from certain species of marine red algae (Rhodophyta) [1]. They are composed of alternating 3-linked β-D-galactopyranose (G-units) and 4-linked α-D-galactopyranose (D-units) or 4-linked 3,6-anhydro-α-D-galactopyranose (DA-units), forming the disaccharide repeating unit of carrageenans (Figure 1). The sulphated galactans are classified according to the presence of the 3,6-anhydro-bridge on the 4-linked galactose residue and the position and number of sulphate groups. The most common types of carrageenan are traditionally identified by a Greek prefix indicating the major component of the sample. To describe more complex carrageenan structures a uniform letter code nomenclature has been developed by Knutsen et al. [2]. The three commercially most important carrageenans are called ι (iota)-, κ (kappa)-, and λ (lambda)-carrageenan, the corresponding letter codes are G4S-DA2S, G4S-DA, and G2S-D2S,6S. Two other types, called μ (mu)- and ν (nu)-carrageenan, which are the biological precursors of respectively κ- and ι-carrageenan, are often encountered in commercial carrageenan.