Innovative safer drugs translating biophysics advances
Our scientific breakthroughs in the field of molecular biophysics provide the foundation for the innovative technologies we are currently implementing at Ariel Fernandez Consultancy to improve drug design. For more than a decade we have been focusing on the development of a multi-scale theory of the biological interface, the complex solvent region sustained beyond the surface of a target protein. These efforts have been fueled by our earlier observation that the interface of a soluble protein, and not its structure!, is the real target in molecular therapy. In this regard, at Ariel Fernandez Consultancy a good portion of our scientific program is geared at answering a fundamental question: What structural features of soluble proteins introduce distortions in the water matrix? The physico-chemical apparatus deployed at Ariel Fernandez Consultancy to address this question paved the way to a considerable output of scientific breakthroughs that started with the discovery of the dehydron. A dehydron is a packing defect in a protein consisting of a water-exposed backbone hydrogen bond. The dehydron introduces a significant distortion of the water matrix, hence generating protein-water interfacial tension. It is a structural vulnerability and most crucially, it is a targetable unique feature that enables us to tell apart desirable therapeutic targets from unwanted targets implicated in side effects. Thus, the dehydron pattern of a protein constitutes a formidable selectivity filter that enables us at Ariel Fernandez Consultancy to distinguish closely related proteins with common ancestry but different functionality (the so-called paralogs). The discovery of the dehydron literally triggered a paradigm shift in drug design, as it heralded a new generation of chemical compounds capable of "wrapping" the unique packing defects in the target protein, thereby curbing the protein-water interfacial tension. This line of thinking lead to the advent of the so-called "wrapping technology", an innovation of unfathomable possibilities when coupled with new and creative ways of parsing chemical space in search for dehydron-wrapping compounds. As the reader can easily grasp, at Ariel Fernandez Consultancy we are advocating a rational approach to drug design based on a novel selectivity feature that enables an exquisite control of the reactivity profile of a therapeutic agent.