Focal Point: Medicinal Chemistry: A. Ligand-Receptor Interactions: From Understanding to Design

Authors

  • Gerd Folkers
  • Manfred Kansy

DOI:

https://doi.org/10.2533/000942903777679677

Keywords:

Antigen presentation, Biomolecular nmr, Cell-based therapy, Computational chemistry, Computer-assisted ligand design, Database mining, Drug design, Drug targets, Genetic switch, Ligand binding mode, Ligand-protein interactions, Nmr screening, Pharmacophore, Reporter ligand, Stem cells, Structure-based drug design, Suicide gene, Therapeutic gene, Virtual libraries

Abstract

The ultimate step in drug action is its interaction with the biological target. This process governed by physicochemical forces, should be as specific as possible. High specificity paired by high affinity is one of the main pillars of a safe drug. In a rational approach the close integration of biophysical analytics, molecular biology and functional genomics and computational chemistry leads to a deep understanding of ligand–protein interaction at the molecular level. Switching forth and back between the virtual and real world, modern design processes allow for the creation of sophisticated ligands for the benefits of future therapeutic intervention. This situation was reflected in the talks of four speakers of the morning session at the symposium having the focus on medicinal chemistry.In his compelling style Hugo Kubinyi gave a comprehensive overview on ligand–receptor interactions. Besides teaching the basics, numerous examples coming from his rich and life-long experience in drug design pointed out both scope and limitations of the actual approaches in drug design.Osman Güner from Accelrys was not able to come but was substituted by the European representative Remy Hofmann, who has longstanding experience in computational chemistry, especially focusing in the 3D-QSAR and pharmacophore description. His talk summarized the current approaches and provided insight in future developments which could soon facilitate categorization processes based on pharmacophoric properties for huge compound databases.In the third talk, Leonardo Scapozza from the Institute of Pharmacy of the ETHZ delivered a fascinating and exciting research case from his lab. Based on the highly integrated technology mentioned above he designs therapeutic genes for application in cell-based therapy. By use of these 'genetic switches' one might be able in future to control graft-versus-host reactions after tissue transplants. Not only the protein, designed to avoid immune recognition and delivered via stem-cells, but also the adequate ligand has been designed to specifically interact on demand.The end of the session was marked by Wolfgang Jahnke, showing us the exciting new applications of nuclear magnetic resonance methodology. Especially for detailed studies in the life sciences – recently acknowledged by the Nobel price granted to Kurt Wüthrich – NMR seems to develop as the ultimate technology.

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Published

2003-01-01

How to Cite

[1]
G. Folkers, M. Kansy, Chimia 2003, 57, 57, DOI: 10.2533/000942903777679677.