Chemistry Reference
In-Depth Information
INTRODUCTION
It is known that most biological processes are essentially dependent on the
interactions that occur between
macromolecules in the living organisms
and small
molecules, which can be synthesized or natural compounds. It means that
biological functions are promoted or inhibited by the interaction of biomolecules
with their ligands. Thus, a deep knowledge of how the binding processes occur
(cellular recognition, cell-antigens recognition, hormone-receptor interaction,
drug-receptor interaction,
etc.
) is indispensable for a better understanding of the
biological systems and even for specific interventions [1-3].
Considering this context, X-ray crystallography and Nuclear Magnetic Resonance
(NMR) spectroscopy have been important tools to provide detailed structural
information regarding the ligand-target complex. Commonly, X-ray
crystallography is used to determine the structure of biological macromolecules,
mainly protein and nucleic acids (DNA and RNA), but it is useful only for those
that can be coaxed into a crystalline state. However, when a complex cannot be
crystallized, NMR spectroscopy can be used to obtain structural information in
solution, as it really is in biological systems [1, 4, 5].
Over past decades, NMR spectroscopy ceased to be an analytical technique
designed only to investigate the structure of small compounds. In recent years,
great improvements in NMR technology have enabled it to be an attractive tool
for the study of high- and low-affinity biomolecular interactions between protein-
protein, protein-nucleic acid and protein-ligand [6-8]. NMR is considered a
versatile biophysical technique since it detects and quantifies molecular
interactions in solution at atomic level through experiments that can indicate and
characterize binding events by looking at the resonance signals of the ligand or
the protein. Besides providing detailed structural information, NMR is unique in
its ability to provide thermodynamic and kinetic aspects of a binding reaction in
macromolecular complexes [3, 7, 9-11].
Probably, the most impacting and benefiting result of these advances in the NMR
spectroscopy has been observed in its wide application in drug discovery process
in the academy and pharmaceutical industry. U
ndoubtedly, the process to identify
