Small molecule

From Wikipedia, the free encyclopedia

In pharmacology and biochemistry, a small molecule is an organic compound that is not a polymer. Biopolymers such as nucleic acids, proteins, and polysaccharides (such as starch or cellulose) are not small molecules, although their constituent monomers—ribo- or deoxyribonucleotides, amino acids, and monosaccharides, respectively—are often considered to be. Very small oligomers are also usually considered small molecules, such as dinucleotides, peptides such as the antioxidant glutathione, and disaccharides such as sucrose.

While small molecules almost always have a lower molecular weight than biopolymers, a very small protein with a defined fold, such as the artificial ten-amino-acid protein chignolin[1], can indeed be smaller than some exceptionally large small molecules such as triglycerides.

Small molecules can have a variety of biological functions, serving as cell signalling molecules, as tools in molecular biology, as drugs in medicine, and in countless other roles. 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).

[edit] 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 membranes. Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as prodrugs.
Many dietary supplements are small molecules (but not herb extracts, such as ginkgo).

[edit] 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).

• Alkaloids
• Glycosides
• Lipids
• Flavonoids
• Nonribosomal peptides, such as actinomycin-D
• Phenazines
• Phenols
• Polyketide
• Terpenes, including steroids
• Tetrapyrroles

[edit] 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 ^[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 the 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]

Binding of ligand can be characterised using a variety of analytical techniques such as surface plasmon resonance or dual polarisation interferometry to quantify the reaction affinities and kinetic properties and also any induced conformational change.

[edit] See also

• Chemical compound microarray
• Chemogenomics
• Peptidomimetic

[edit] References