Small molecules

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In pharmacology, a small molecule is a small organic compound that is biologically active (biomolecule) but is not a polymer. This term is very loosely used and it may or may not include monomers or primary metabolites, in fact it is generally used to denote molecules that are not protein which play a endogenous or exogenous biological role, such as cell signalling, are used as a tool in molecular biology or are a drug in medicine.

These compounds can be natural (such as secondary metabolites) or artificial (such as antiviral drugs); they may have a beneficial effect against a disease (such as FDA approved drugs) or may be detrimental (such as teratogens and carcinogens).

Contents

Drugs

Most drugs are small molecules, although some drugs can be proteins, e.g. insulin. Many proteins are degraded if administered orally and most often cannot cross the cell membrane. This is often not the case for small molecules, some though of which are orally available as a Prodrug. Many dietary supplements are small molecules (but not herb extracts, such as ginkgo).

For the discovery of natural small molecules for pharmaceutical use, see Biomining.
For the creation of artificial small molecules for pharmaceutical use, see drug design.

Secondary metabolites

For organisms to produce small molecules they need one or more specialized enzymes (to create and destroy), which as a result are not that abundant in vertebrates (recent and small + slow population size), but very common in soil bacteria (such as streptomyces) and fungi, which in particular secrete antibiotics.

Plants also have several secondary metabolites, which play a role in cell signalling, pigmentation or in defence, several of which have also been used as drugs (medical and recreational).

Investigative tools

A further example, Cell culture example of small molecules as a tool instead of a protein. in cell culture to obtain a pancreatic lineage from mesodermal stem cells the retinoic acid signalling pathway must be activated while the sonic hedgehog pathway inhibited, which can be done by adding to the media anti-shh antibodies, Hedgehog interacting protein or cyclopamine, the first two are protein and the last a small molecule .
A further example, Cell culture example of small molecules as a tool instead of a protein. in cell culture to obtain a pancreatic lineage from mesodermal stem cells the retinoic acid signalling pathway must be activated while the sonic hedgehog pathway inhibited, which can be done by adding to the media anti-shh antibodies, Hedgehog interacting protein or cyclopamine, the first two are protein and the last a small molecule [1].

Enzymes and receptors are often activated or inhibited by endogenous protein, but can be also inhibited by endogenous or exogenous small molecule inhibitors or activators with can bind to the active site or on allosteric site.

An example is the teratogen and carcinogen phorbol 12-myristate 13-acetate which is a plant terpene which activates protein kinase C resulting in cancer, making it a very useful investigative tool.[2] There is also interest in creating small molecule artificial transcription factors to regulate gene expression, examples include wrenchnol (a wrench shaped molecule). [3]

See also

References

  1. ^ Mfopoua, J. K., De Grootea, V., Xub, X., Heimbergb, H., & Bouwensa, L. (2007). Sonic Hedgehog and Other Soluble Factors from Differentiating Embryoid Bodies Inhibit Pancreas Development. Stem Cell , 25, 1156–1165.
  2. ^ Voet and Voet (1995) Biochemistry, 2nd ed., John Wiley & Sons, Inc., New York, NY
  3. ^ Koh JT, Zheng J (September 2007). "The new biomimetic chemistry: artificial transcription factors". ACS Chem. Biol. 2 (9): 599–601. doi:10.1021/cb700183s. PMID 17894442. 

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  • This page was last modified on 15 September 2008, at 13:59.

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