1Max-Planck-Institut für Biochemie, Emeritusgruppe Strukturforschung, D-82152 Martinsried
2Technische Universität München, TUM Emeritus of Excellence, D-85747 Garching
3Universität Duisburg-Essen, Zentrum für Medizinische Biotechnologie, D-45117 Essen
The design and development of small molecules and biologicals as drugs and components for therapies in medicine is assisted essentially by knowledge of the three-dimensional structures of the physiological players involved, the ligands and their targets. Structural information preferably at atomic resolution lies the basis for understanding function and chemistry of their interactions.
The last decades and the past century presented us with revolutionary methods and instruments to study biological molecules at high resolution. They are based on research in physics, chemistry and biology and medicine, academic endeavors that were frequently honoured with Nobel Prizes and began with the discovery of X-rays.
From the point of view of structural biology one can describe the 20th century of “extended vision”. Of course, the desire and the effort to see the far and the near was alive long before X-rays. Astronomy was the first science to use optical aids, the telescopes, to observe the stars and their orbits. There is much evidence of the fascination with the new possibilities of observing the sky, such as the quote from R. Descartes (1637): "By taking our sense of sight far beyond the realm of our forbears' imagination, these wonderful instruments, the telescopes, open the way to a deeper and more perfect understanding of nature”. His remark applies equally to biological objects and to the microscopes that were being developed at the same time. R. Hooke (1665) gives free rein to his enthusiasm and draws a link to technical developments of microscopes and seeing small things on earth: “By the invention of optical glasses and by the means of telescopes, there is nothing so far distant but may be represented to our view; and by the help of microscopes, there is nothing so small as to escape our inquiry; Hence there is a new visible world discovered to the understanding” in Micrographia, or some Physiological Descriptions of Minute Bodies made by Magnifying Glasses with Observations and Inquiries thereupon. (Huber, R., Bochtler, M., (2022). „Das Jahrhundert des Sehens“. In Lohse, M., „Wenn der Funkte überspringt – 200 Jahre Gesellschaft Deutscher Naturforscher und Ärzte“ (S. 78 – 85). Leipzig: Passage-Verlag).
The discovery of novel strategies and drugs and their benefits for patients provided a strong motivation for the expansion of the activity of big pharma enterprises and the foundation of specialized commercial enterprises with a focus on novel methods and chemical entities. This latter activity I will illustrate with three examples and spin-offs involving my own work, their underlying research and discoveries, and the foundation and development of their businesses:
Proteros biostructures (www.Proteros.com), a provider of structure-based early-stage drug discovery services.
SuppreMol (www.SuppreMol), a privately held biotechnology company that pioneers a novel approach for the treatment of autoimmune diseases.
QLi5 Therapeutics (www.QLi5 Therapeutics.com), a biotechnology company and developer of a new class of proteasome inhibitors with an unprecedented, non-covalent mode of action.