Chemical genetics

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The aim of genetics is to decipher how genes influence life processes . The Chemical Genetics , even chemo Genetics ( Engl. : Chemo genetics ) called, however, the goal of pursuing the function of the gene products, ie the proteins to elucidate with the help of chemical substances.

Chemical genetics is the study of individual gene products (proteins) using a combination of chemical and biological methods. In chemical genomics , on the other hand, the products of a gene family are examined.

background

Of the estimated 100,000 proteins that are encoded by DNA in the human body , the chemical structure of only 500 is known. In chemical genetics, low molecular weight compounds (so-called small molecules ) are used as protein ligands to explain basic biochemical processes and the function of the proteins involved. After the largely completed sequencing of the human genome ( Human Genome Project ) and the many model organisms , is now elucidating the function of genes, or their products, the proteins, the focus of Biochemistry . Chemical genetics is a promising approach to this.

The low molecular weight compounds are often natural substances or modified natural substances or substances produced by combinatorial chemistry. With the help of combinatorial chemistry , a large number of different chemical compounds, a so-called molecule library , can be generated and also tested using high throughput screening .

Stuart Schreiber and Tim J. Mitchison were the first to describe the essential elements for chemical genetics.

In addition to explaining the function of individual proteins, chemical genetics is also used to develop new drugs .

Differentiation from other genetic procedures

Chemical genetics differs from other genetic methods, such as mutation genetics or the knockout technique , in a number of advantages:

  • Small molecules act quickly after administration.
  • The biological effect is by metabolism ( metabolism usually reversible). This enables time-dependent (dynamic) functional tests on proteins.
  • The effect can be influenced via the concentration of the active substance and thus different manifestations of the phenotype can be achieved.
  • The effect can be examined in the organism at any point in time of its development. The effects of a gene knockout, which is lethal in the embryonic stage, cannot be investigated in the adult organism.
  • Knockout studies cannot differentiate proteins derived from the same gene.
  • The effect can be reproduced anytime and anywhere.

Individual evidence

  1. ↑ a b c Max Planck Society: Searching for active substances with molecular probes. dated January 26, 2005.
  2. ↑ a b c R. Breinbauer: Chemical genetics discovered (zebra) fishing. In: Angewandte Chemie 115/2003, pp. 1116-1118.
  3. ^ SL Schreiber: Chemical genetics resulting from a passion for synthetic organic chemistry. Bio. Med. Chem. 6/1998, pp. 1127-1152. PMID 9784856
  4. ^ TJ Mitchison: Towards a pharmacological genetics. In: Chem. Biol. 1/1994, pp. 3-6. PMID 9383364 .
  5. ^ L. Weber: Chemistry for Chemical Genomics. In: Methods in Molecular Biology 310/2005, pp. 11-24. doi : 10.1007 / 978-1-59259-948-6 .

further reading

  • H. Kubinyi (Editor) et al: Chemogenomics in Drug Discovery: A Medicinal Chemistry Perspective. Wiley-VCH, 2004, ISBN 3-527-30987-X
  • S. Jaroch: Chemical Genomics: Small Molecule Probes to Study Cellular Function. Springer, 2008, ISBN 3-540-27865-6
  • F. Darvas et al: Chemical Genomics. Marcel Dekker, 2004
  • FR Salemme: Chemical genomics as an emerging paradigm for postgenomic drug discovery. In: Pharmacogenomics 4/2003, pp. 1-11.
  • CM Crews and U. Splittgerber: Chemical genetics: exploring and controlling cellular processes with chemical probes. In: TIBS 5/1999, pp. 317-320.
  • SL Schreiber: Target-oriented and diversity-oriented organic synthesis in drug discovery. In: Science 287/2000, pp. 1964-1969.

Web links