A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally but are also synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. Most aromatic polyamines are crystalline solids at room temperature.
Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triamine and tetraamine spermidine and spermine. They are structurally and biosynthetically related to the diamines putrescine and cadaverine. Polyamine metabolism is regulated by the activity of the enzyme ornithine decarboxylase (ODC). Polyamines are found in high concentrations in the mammalian brain.
Several synthetic polyamines are used in chemical industry and the research laboratory. They are mainly of interest as additives to motor oil and as co-reactants (hardeners) with epoxy resins. Many synthetic polyamines feature NCH2CH2N linkages:
- Diethylenetriamine, abbreviated dien or DETA, (H2N-CH2CH2-NH-CH2CH2-NH2. The related permethylated derivative pentamethyldiethylenetriamine is used as a chelating agent in organolithium chemistry.
- Triethylenetetramine (trien or TETA, H2N-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH2), tetraethylenepentamine (TEPA, H2N-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH2), pentaethylenehexamine (PEHA, H2N-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH-CH2CH2-NH2).
- Macrocyclic polyamines: 1,4,7-triazacyclononane ((NHCH2CH2)3) and cyclen ((NHCH2CH2)4). A related tetraaza macrocycle is cyclam.
- Tris(2-aminoethyl)amine (N(CH2CH2NH2)3) is a branched polyamine. A related tripodal polyamine is 1,1,1-tris(aminomethyl)ethane.
Subunit of polyethylenimine
Although it is known that the biosynthesis of polyamines is highly regulated, the biological function of polyamines is only partly elucidated. In their cationic ammonium form, they bind to DNA, and, in structure, they represent compounds with cations that are found at regularly spaced intervals (in contrast to Mg2+
, which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.
Inhibition of polyamine biosynthesis, retards or stops cell growth. The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells express a polyamine-transporting ATPase on their cell membrane that facilitates the internalization of exogenous polyamines. This system is highly active in rapidly proliferating cells and is the target of some chemotherapeutics currently under development.
Polyamines are also modulators of a variety of ion channels, including NMDA receptors and AMPA receptors. They block inward-rectifier potassium channels so that the currents of the channels are inwardly rectified, thereby the cellular energy, i.e. K+
ion gradient across the cell membrane, is conserved. In addition, polyamine participate in initiating the expression of SOS response of Colicin E7 operon and down-regulate proteins that are essential for colicin E7 uptake, thus conferring a survival advantage on colicin-producing E. coli under stress conditions.
Biosynthesis of spermidine, spermine, thermospermine
Thermospermine (NH2-(CH2)3-NH-(CH2)3-NH-(CH2)4-NH2) is a structural isomer of spermine and a novel type of plant growth regulator. It is produced from spermidine by the action of thermospermine synthase, which is encoded by a gene named ACAULIS5 (ACL5).
The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism. These agents are used in cancer therapy. Polyamine analogues upregulate p53 in a cell leading to restriction of proliferation and apoptosis. It also decreases the expression of estrogen receptor alpha in ER-positive breast cancer.
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