Chemical Genetics

Chemical Genetics is the investigation of the function of proteins and signal transduction pathways in cells by the screening of chemical libraries of small molecules. Chemical genetics is analogous to classical genetic screen where random mutations are introduced in organisms, the phenotype of these mutants is observed, and finally the specific gene mutation (genotype) that produced that Phenotype is identified. In chemical genetics, the phenotype is disturbed not by introduction of mutations, but by exposure to small molecule tool compounds. Phenotypic screening of chemical libraries is used to identify drug targets (forward genetics) or to validate those targets in experimental models of disease (reverse genetics).

Chemical Biology
Chemical Biology is a scientific discipline spanning the fields of chemistry and biology. The discipline involves the application of chemical techniques, analysis, and often small molecules produced through synthetic chemistry, to the study and manipulation of biological systems. In contrast to biochemistry, which involves the study of the chemistry of biomolecules and regulation of biochemical pathways within and between cells, chemical biology deals with chemistry applied to biology (synthesis of biomolecules, simulation of biological systems etc.).

Directed evolution
A primary goal of Protein Engineering is the design of novel peptides or Proteins with a desired structure and chemical activity. Because our knowledge of the relationship between primary sequence, structure, and function of proteins is limited, rational design of new proteins with engineered activities is extremely challenging. In directed evolution, repeated cycles of genetic diversification followed by a screening or selection process, can be used to mimic natural selection in the laboratory to design new proteins with a desired activity.

Drug Discovery to Pharma
The chemical genetic approach uses techniques that have been widely applied in drug discovery for a long time and adapts them to the study of biological problems. The earliest drugs, which have been used empirically for centuries, were mostly natural compounds that were discovered by chance. In most cases, humans or animals ingested, drank or were accidentally exposed to herbal or fungal substances and a useful effect was observed. Retrospectively, one could see this trial and error approach as an unbiased Phenotype-based screen. The first progress toward a systematic approach to drug development was done in the late eighteenth century, when active agents were routinely purified from plant extracts (like opium from the opium poppy or digitalis, a drug used for heart failure, from the foxglove plant). At that time, the concept that the effect of plant extracts is mediated by their single constituents was shaped. In 1827, Emanuel Merck introduced morphine, a naturally occurring alkaloid, as the first commercially available pure drug in large-scale production. This was the starting point for the rise of pharmaceutical companies during the 20th century. By chemical synthesis, they accumulated giant “libraries” of compounds that were screened in different assays for their effectivity as drugs. This strategy for drug development dominated the 20th century and is what we know today as traditional medicinal chemistry.