Sánchez Pedregal

We use solution Nuclear Magnetic Resonance (NMR) to solve chemical and biological questions.

The structure of molecules reveals important aspects of their behaviour, and help us to understand the function of biomolecules in vivo or to develop new molecules with useful properties, such as therapeutic drugs.

Biomolecules. Ligand/receptor molecular recognition.

NMR can be used to analyze the transient binding of a ligand (typically a small molecule) to its biomolecular receptor (typically a protein). A well-established application is the detection of hits for a drug target in the field of drug discovery. With experiments such as tr-NOE (transferred NOE) or STD, we can characterize the interaction, the binding epitopes and the conformational changes that take place upon association of ligands to their receptors.

Furthermore, when the ligand/receptor complex is stable enough, and provided the overall molecular mass is of moderate size, we can determine the three-dimensional structure of such complex by NMR.

At present we are studying complexes of oligo-DNA with ligands that bind to the minor groove

Organic molecules. Application of Residual Dipolar Couplings to conformational analysis.

The conformational analysis of organic molecules is usually based on angular and distance restraints derived from the measurement of NMR observables such as scalar couplings (3J) and NOE intensities.

It often happens that these restraints are scarce and do not suffice to determine the conformation of flexible molecules. In the last decade, Residual Dipolar Couplings have proven very useful for the structural study of small molecules.

We are currently working on the application of RDC for the analysis of molecules in conformational equilibrium, both in organic and aqueous solution.