Within the fields of
molecular biology
Molecular biology is the branch of biology that seeks to understand the molecular basis of biological activity in and between cells, including biomolecular synthesis, modification, mechanisms, and interactions. The study of chemical and physi ...
and
pharmacology, a small molecule or micromolecule is a low molecular weight (≤ 1000
daltons)
organic compound
In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. T ...
that may regulate a biological process, with a size on the order of 1 nm. Many
drugs are small molecules; the terms are equivalent in the literature.
Larger structures such as
nucleic acids and
protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, res ...
s, and many
polysaccharides
Polysaccharides (), or polycarbohydrates, are the most abundant carbohydrates found in food. They are long chain polymeric carbohydrates composed of monosaccharide units bound together by glycosidic linkages. This carbohydrate can react with w ...
are not small molecules, although their constituent monomers (ribo- or deoxyribonucleotides,
amino acid
Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha a ...
s, and monosaccharides, respectively) are often considered small molecules. Small molecules may be used as research tools to probe
biological function
In evolutionary biology, function is the reason some object or process occurred in a system that evolved through natural selection. That reason is typically that it achieves some result, such as that chlorophyll helps to capture the energy of sunl ...
as well as
leads in the development of new
therapeutic agents. Some can inhibit a specific function of a protein or disrupt
protein–protein interaction
Protein–protein interactions (PPIs) are physical contacts of high specificity established between two or more protein molecules as a result of biochemical events steered by interactions that include electrostatic forces, hydrogen bonding and th ...
s.
Pharmacology usually restricts the term "small molecule" to molecules that bind specific biological
macromolecules
A macromolecule is a very large molecule important to biophysical processes, such as a protein or nucleic acid. It is composed of thousands of covalently bonded atoms. Many macromolecules are polymers of smaller molecules called monomers. The ...
and act as an
effector
Effector may refer to:
*Effector (biology), a molecule that binds to a protein and thereby alters the activity of that protein
* ''Effector'' (album), a music album by the Experimental Techno group Download
* ''EFFector'', a publication of the El ...
, altering the activity or function of the
target. Small molecules can have a variety of biological functions or applications, serving as
cell signaling
In biology, cell signaling (cell signalling in British English) or cell communication is the ability of a cell to receive, process, and transmit signals with its environment and with itself. Cell signaling is a fundamental property of all cellula ...
molecules,
drugs in
medicine
Medicine is the science and practice of caring for a patient, managing the diagnosis, prognosis, prevention, treatment, palliation of their injury or disease, and promoting their health. Medicine encompasses a variety of health care pr ...
,
pesticides in farming, and in many other roles. These compounds can be natural (such as
secondary metabolites
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the nor ...
) or artificial (such as
antiviral drugs); they may have a beneficial effect against a disease (such as
drugs) or may be detrimental (such as
teratogens and
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subs ...
s).
Molecular weight cutoff
The upper
molecular-weight
The molecular mass (''m'') is the mass of a given molecule: it is measured in daltons (Da or u). Different molecules of the same compound may have different molecular masses because they contain different isotopes of an element. The related quanti ...
limit for a small molecule is approximately 900 daltons, which allows for the possibility to rapidly diffuse across cell membranes so that it can reach
intracellular
This glossary of biology terms is a list of definitions of fundamental terms and concepts used in biology, the study of life and of living organisms. It is intended as introductory material for novices; for more specific and technical definitions ...
sites of action.
This molecular weight cutoff is also a necessary but insufficient condition for oral
bioavailability
In pharmacology, bioavailability is a subcategory of absorption and is the fraction (%) of an administered drug that reaches the systemic circulation.
By definition, when a medication is administered intravenously, its bioavailability is 100%. Ho ...
as it allows for
transcellular transport through intestinal
epithelial
Epithelium or epithelial tissue is one of the four basic types of animal tissue, along with connective tissue, muscle tissue and nervous tissue. It is a thin, continuous, protective layer of compactly packed cells with a little intercell ...
cells. In addition to intestinal permeability, the molecule must also possess a reasonably rapid
rate of dissolution into water and adequate water
solubility
In chemistry, solubility is the ability of a substance, the solute, to form a solution with another substance, the solvent. Insolubility is the opposite property, the inability of the solute to form such a solution.
The extent of the solub ...
and moderate to low
first pass metabolism. A somewhat lower molecular weight cutoff of 500 daltons (as part of the "
rule of five") has been recommended for oral small molecule drug candidates based on the observation that clinical attrition rates are significantly reduced if the molecular weight is kept below this limit.
Drugs
Most pharmaceuticals are small molecules, although some drugs can be proteins (e.g.,
insulin and other
biologic medical products). With the exception of
therapeutic antibodies, many proteins are degraded if administered orally and most often cannot cross
cell membrane
The cell membrane (also known as the plasma membrane (PM) or cytoplasmic membrane, and historically referred to as the plasmalemma) is a biological membrane that separates and protects the interior of all cells from the outside environment ( ...
s. Small molecules are more likely to be absorbed, although some of them are only absorbed after oral administration if given as
prodrugs. One advantage that small molecule drugs (SMDs) have over "large molecule"
biologics is that many small molecules can be taken orally whereas biologics generally require injection or another
parenteral administration.
Secondary metabolites
A variety of organisms including bacteria, fungi, and plants, produce small molecule
secondary metabolite
Secondary metabolites, also called specialised metabolites, toxins, secondary products, or natural products, are organic compounds produced by any lifeform, e.g. bacteria, fungi, animals, or plants, which are not directly involved in the norma ...
s also known as
natural products, which play a role in cell signaling, pigmentation and in defense against predation. Secondary metabolites are a rich source of biologically active compounds and hence are often used as research tools and leads for drug discovery.
Examples of secondary metabolites include:
*
Alkaloids
*
Glycosides
*
Lipids
Lipids are a broad group of naturally-occurring molecules which includes fats, waxes, sterols, fat-soluble vitamins (such as vitamins A, D, E and K), monoglycerides, diglycerides, phospholipids, and others. The functions of lipids include ...
*
Nonribosomal peptides, such as
actinomycin-D
*
Phenazines
*
Natural phenols (including
flavonoids)
*
Polyketide
Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...
*
Terpenes
Terpenes () are a class of natural products consisting of compounds with the formula (C5H8)n for n > 1. Comprising more than 30,000 compounds, these unsaturated hydrocarbons are produced predominantly by plants, particularly conifers. Terpenes ar ...
, including
steroids
*
Tetrapyrroles
Tetrapyrroles are a class of chemical compounds that contain four pyrrole or pyrrole-like rings. The pyrrole/pyrrole derivatives are linked by ( =- or -- units), in either a linear or a cyclic fashion. Pyrroles are a five-atom ring with four car ...
.
Research tools
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, which can bind to the
active site or on the
allosteric site
In biochemistry, allosteric regulation (or allosteric control) is the regulation of an enzyme by binding an effector molecule at a site other than the enzyme's active site.
The site to which the effector binds is termed the ''allosteric site ...
.
An example is the teratogen and carcinogen
phorbol 12-myristate 13-acetate, which is a plant terpene that activates
protein kinase C, which promotes cancer, making it a useful investigative tool.
There is also interest in creating small molecule
artificial transcription factors to regulate
gene expression, examples include wrenchnolol (a wrench shaped molecule).
Binding of
ligand
In coordination chemistry, a ligand is an ion or molecule ( functional group) that binds to a central metal atom to form a coordination complex. The bonding with the metal generally involves formal donation of one or more of the ligand's elec ...
can be characterised using a variety of analytical techniques such as
surface plasmon resonance
Surface plasmon resonance (SPR) is the resonant oscillation of conduction electrons at the interface between negative and positive permittivity material in a particle stimulated by incident light. SPR is the basis of many standard tools for measu ...
,
microscale thermophoresis
Microscale thermophoresis (MST) is a technology for the biophysical analysis of interactions between biomolecules. Microscale thermophoresis is based on the detection of a temperature-induced change in fluorescence of a target as a function of th ...
or
dual polarisation interferometry
Dual-polarization interferometry (DPI) is an analytical technique that probes molecular layers adsorbed to the surface of a waveguide using the evanescent wave of a laser beam. It is used to measure the conformational change in proteins, or othe ...
to quantify the reaction affinities and kinetic properties and also any induced
conformational changes.
Anti-genomic therapeutics
Small-molecule
anti-genomic therapeutics, or SMAT, refers to a
biodefense technology that targets
DNA signatures found in many
biological warfare
Biological warfare, also known as germ warfare, is the use of biological toxins or infectious agents such as bacteria, viruses, insects, and fungi with the intent to kill, harm or incapacitate humans, animals or plants as an act of war. ...
agents. SMATs are new, broad-spectrum drugs that unify antibacterial, antiviral and anti-malarial activities into a single therapeutic that offers substantial cost benefits and logistic advantages for physicians and the military.
See also
*
Pharmacology
*
Druglikeness
*
Lipinski's rule of five
Lipinski's rule of five, also known as Pfizer's rule of five or simply the rule of five (RO5), is a rule of thumb to evaluate druglikeness or determine if a chemical compound with a certain pharmacological or biological activity has chemical pro ...
*
Metabolite
*
Chemogenomics
*
Neurotransmitter
*
Peptidomimetic
A peptidomimetic is a small protein-like chain designed to mimic a peptide. They typically arise either from modification of an existing peptide, or by designing similar systems that mimic peptides, such as peptoids and β-peptides. Irrespective ...
*
Macromolecule
References
External links
* {{MeSH name, Small+Molecule+Libraries
Plant physiology
Drug discovery
Induced stem cells