Differential scanning calorimetry in life science: thermodynamics, stability, molecular recognition and application in drug design

All biological phenomena depend on molecular recognition, which is either intermolecular like in ligand binding to a macromolecule or intramolecular like in protein folding. As a result, understanding the relationship between the structure of proteins and the energetics of their stability and binding with others (bio)molecules is a very interesting point in biochemistry and biotechnology. It is essential to the engineering of stable proteins and to the structure-based design of pharmaceutical ligands. The parameter generally used to characterize the stability of a system (the folded and unfolded state of the protein for example) is the equilibrium constant (K) or the free energy (deltaG(o)), which is the sum of enthalpic (deltaH(o)) and entropic (deltaS(o)) terms. These parameters are temperature dependent through the heat capacity change (deltaCp). The thermodynamic parameters deltaH(o) and deltaCp can be derived from spectroscopic experiments, using the van't Hoff method, or measured directly using calorimetry. Along with isothermal titration calorimetry (ITC), differential scanning calorimetry (DSC) is a powerful method, less described than ITC, for measuring directly the thermodynamic parameters which characterize biomolecules. In this article, we summarize the principal thermodynamics parameters, describe the DSC approach and review some systems to which it has been applied. DSC is much used for the study of the stability and the folding of biomolecules, but it can also be applied in order to understand biomolecular interactions and can thus be an interesting technique in the process of drug design.

Easy preoperative planning of deeply located brain lesions using external skin reference and 3-Dimensional surface MRI

Open skull surgery of deeply located intracerebral lesions requires precise determination of the treatment area in 3-dimensional (3-D) space. 3-D MRI can give important additional information in presurgical determination of the surgical approach to the target, taking into account highly functional brain areas and important vascular structures. The day before surgery, a grid composed of 9 tubings intersecting at 90° at 1 cm intervals and filled with a Q1SO4 solution is firmly attached to the skin of the patient’s head in the presumed region of the craniotomy. A 3-D turbo-FLASH sequence is then performed in the sagittal plane after intravenous Gd-DOTA injection on a IT Magnetom. 3-D surface reconstruction of the cortical gyri and sulci is performed. Once the gyri are identified, the 3-D program is then implemented in order to perform a color display of the cortical veins and of the tumor boundaries. The surgical access is then chosen by the surgeon, taking into account highly functional areas. Finally, the boundaries of the tumor are projected on the cortex reconstruction and on the external reference placed on the skin. The entry place for surgery as well as the size of craniotomy are drawn on the skin and the tubed grid is removed. The accuracy of this method tested in 9 patients with deeply located brain tumors or arteriovenous malformations was very satisfactory. In daily practice, this method is a valuable technique providing important clinical information in determining the shortest and safest way through the brain tissue, decreasing possible functional deficit and reducing craniotomy size in cases of difficult to access deep brain areas. Our method does not require a stereotactic frame permanently fixed to the head of the patient during surgery. © 1994 S. Karger AG, Basel.