{{Short description|Type of organic compound}} {{distinguish|diamine}} A '''polyamine''' is an organic compound having three or more amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives.<ref name=Ullmann>{{Ullmann|first1=Karsten|last1=Eller|first2=Erhard|last2=Henkes|first3=Roland|last3=Rossbacher|first4=Hartmut|last4=Höke|title=Amines, Aliphatic|year=2005|doi=10.1002/14356007.a02_001}}</ref><ref>Jastrzab, R., Kaczmarek, M.T., Nowak, M., Trojanowska, A., Zabiszak, M. [https://doi.org/10.1016/j.ccr.2017.05.001 "Complexes of polyamines and their derivatives as living system active compounds"]''Coordination Chemistry Reviews'', 2017, 351, pp. 32–44 [https://doi.org/10.1016/j.ccr.2017.05.001 doi.org/10.1016/j.ccr.2017.05.001]</ref> Most aromatic polyamines are crystalline solids at room temperature.
==Natural polyamines== Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triamine spermidine and the tetraamine 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).<ref name=Pegg>{{cite journal| title=Polyamine metabolism and function| first1=AE| last1=Pegg| first2=PP| last2=McCann| journal=American Journal of Physiology| year=1982| volume=243| issue=5| pages=212–221| pmid=6814260| doi=10.1152/ajpcell.1982.243.5.C212| s2cid=21063248}}</ref> Polyamines are found in high concentrations in the mammalian brain.<ref name=Seiler>{{cite book |first=N. |last=Seiler |chapter=Polyamines |chapter-url=https://link.springer.com/chapter/10.1007/978-1-4757-0614-7_9 |editor-last=Lajtha |editor-first=A. |title=Chemical and Cellular Architecture |series=Handbook of Neurochemistry |volume=1 |publisher=Springer |edition=2nd |date=1982 |isbn=978-1-4757-0614-7 |pages=223–255 |doi=10.1007/978-1-4757-0614-7_9}}</ref>
<gallery caption="Natural polyamines" widths="180px" heights="120px"> File:Spermidine-2D-skeletal.svg|spermidine File:Spermine.svg|spermine </gallery>
===Biological function=== Although it is known that the biosynthesis of polyamines is highly regulated, the biological function of polyamines is only partly understood. 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 {{chem|Mg|2+|link=Mg ion (physiology)}} or {{chem|Ca|2+|link=Calcium in biology}}, which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.<ref>{{cite journal|author1=Rato C |author2=Amirova S.R |author3=Bates D.G |author4=Stansfield I |author5=Wallace H.M |title=Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift|journal=Nucleic Acids Res.|volume=39|issue=11|pages=4587–97|date=June 2011|doi=10.1093/nar/gkq1349|pmid=21303766|pmc=3113565}}</ref>
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.<ref>{{cite journal |vauthors=Wang C, Delcros JG, Cannon L, Konate F, Carias H, Biggerstaff J, Gardner RA, Phanstiel IV O |title=Defining the molecular requirements for the selective delivery of polyamine conjugates into cells containing active polyamine transporters |journal=J Med Chem |volume=46 |issue=24 |pages=5129–38 |date=November 2003 |pmid=14613316 |doi=10.1021/jm030223a }}</ref>
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. {{chem|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.<ref>{{cite journal |author1=Yi-Hsuan Pan |author2=Chen-Chung Liao |title=The critical roles of polyamines regulating ColE7 production and restricting ColE7 uptake of the colicin-producing Escherichia coli|journal=J. Biol. Chem. |volume=281|pages=13083–91 |date=May 2006 |pmid=16549429 |issue=19 |doi=10.1074/jbc.M511365200| doi-access=free }}</ref>
Polyamines can enhance the permeability of the blood–brain barrier.<ref>{{cite journal |vauthors=Zhang L, Lee HK, Pruess TH, White HS, Bulaj G |title=Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin |journal=J. Med. Chem. |volume=52 |issue=6 |pages=1514–7 |date=March 2009 |pmid=19236044 |pmc=2694617 |doi=10.1021/jm801481y }}</ref>
They are involved in modulating senescence of organs in plants and are therefore considered as a plant hormone.<ref>{{cite journal |vauthors=Pandey S, Ranade SA, Nagar PK, Kumar N |title=Role of polyamines and ethylene as modulators of plant senescence |journal=J. Biosci. |volume=25 |issue=3 |pages=291–9 |date=September 2000 |pmid=11022232 |doi=10.1007/BF02703938|s2cid=21925829 }}</ref> In addition, they are directly involved in regulation of programmed cell death.<ref>{{cite journal|last=Moschou|first=PN|author2=Roubelakis-Angelakis, KA|title=Polyamines and programmed cell death.|journal=Journal of Experimental Botany|date=Nov 11, 2013|pmid=24218329|doi=10.1093/jxb/ert373|volume=65| issue=5 |pages=1285–96|doi-access=free}}</ref>
===Homology-directed DNA repair=== Polyamines promote homologous recombination (HR)-mediated double-strand break (DSB) repair.<ref name = Lee2019>{{cite journal |vauthors=Lee CY, Su GC, Huang WY, Ko MY, Yeh HY, Chang GD, Lin SJ, Chi P |title=Promotion of homology-directed DNA repair by polyamines |journal=Nat Commun |volume=10 |issue=1 |pages=65 |date=January 2019 |pmid=30622262 |pmc=6325121 |doi=10.1038/s41467-018-08011-1 |bibcode=2019NatCo..10...65L }}</ref> Polyamines enhance the DNA strand exchange activity of RAD51 recombinase. Depletion of polyamines sensitizes cells to genotoxic substances such as ionizing radiation and ultraviolet radiation. The effect of polyamines on RAD51 arises from their ability to enhance the capture of homologous duplex DNA and promote RAD-51-mediated homologous DNA pairing and exchange activity.<ref name = Lee2019/> Polyamines appear to have an evolutionarily conserved role in regulating recombinase activity.
===Biosynthesis of spermidine, spermine, thermospermine=== thumb|400x400px|Biosynthesis of spermidine and spermine from putrescine. Ado = 5'-adenosyl Spermidine is synthesized from putrescine, using an aminopropyl group from decarboxylated ''S''-adenosyl-L-methionine (SAM), ''S''-Adenosylmethioninamine. The reaction is catalyzed by spermidine synthase.<ref name="pmid26089148">{{cite journal | vauthors = Pál M, Szalai G, Janda T | title = Speculation: Polyamines are important in abiotic stress signaling | journal = Plant Science | volume = 237 | pages = 16–23 |date=2015 | doi = 10.1016/j.plantsci.2015.05.003 | pmid = 26089148| bibcode = 2015PlnSc.237...16P | url = http://real.mtak.hu/24396/1/Uneditted.pdf }}</ref>
Spermine is synthesized from the reaction of spermidine with SAM in the presence of the enzyme spermine synthase.
The polyamines undergo rapid interconversion in the polyamine cycle, in which putrescine leads to synthesis of spermidine and spermine, with degradation of these polyamines to form putrescine, which can begin the cycle again.<ref name="pmid26089148" /> {{Clear}}
{{anchor|Thermospermine}}Thermospermine ({{chem2|NH2\s(CH2)3\sNH\s(CH2)3\sNH\s(CH2)4\sNH2}}) is a structural isomer of spermine and a plant growth regulator. It is produced from spermidine by the action of thermospermine synthase, which is encoded by a gene named ACAULIS5 (ACL5).<ref name=Takeno>{{cite journal| title=Thermospermine is not a minor polyamine in the plant kingdom | journal= Plant Cell Physiol| date=April 2012| volume=53| issue=4| pages=606–16| doi=10.1093/pcp/pcs019| pmid=22366038| last1 = Takano | first1 = A | last2 = Kakehi | first2 = J | last3 = Takahashi | first3 = T| url= https://zenodo.org/record/851716| doi-access=free}}</ref>
===Polyamine analogues=== 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.<ref>{{cite journal|title=Role of p53/p21(Waf1/Cip1) in the regulation of polyamine analogue-induced growth inhibition and cell death in human breast cancer cells|journal=Cancer Biology & Therapy|volume=4|issue=9|pages=1006–13|date=September 2005|last1=Huang|first1=Yi|last2=Pledgie|first2=Allison|last3=Rubin|first3=Ethel| last4=Marton|first4=Laurence J.|last5=Woster|first5=Patrick M.|last6=Sukumar|first6=Saraswati|last7=Casero|first7=Robert A.|last8=Davidson|first8=Nancy E.|pmc=3639297|doi=10.4161/cbt.4.9.1970|pmid=16131835}}</ref> It also decreases the expression of estrogen receptor alpha in ER-positive breast cancer.<ref>{{cite journal|title=Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells| pmid=16679312 | doi= 10.1074/jbc.M600910200 | volume=281| issue=28 | pmc=3623667| journal=J Biol Chem| pages=19055–63 | last1 = Huang | first1 = Y | last2 = Keen | first2 = JC | last3 = Pledgie | first3 = A | last4 = Marton | first4 = LJ | last5 = Zhu | first5 = T | last6 = Sukumar | first6 = S | last7 = Park | first7 = BH | last8 = Blair | first8 = B | last9 = Brenner | first9 = K | last10 = Casero | first10 = RA Jr | last11 = Davidson | first11 = NE| year=2006| doi-access=free }}</ref>
==Synthetic polyamines== {{see also|Ethyleneamines}} Ethyleneamines are a commercially-important class of synthetic polyamines with ethylene ({{chem2|\sCH2CH2\s}} linkages); global production capacity was estimated at 385,000 tonnes in 2001.<ref name = kirk>{{Kirk-Othmer | title = Diamines and Higher Amines, Aliphatic | author1 = Srivasan Sridhar | author2 = Richard G. Carter | doi = 10.1002/0471238961.0409011303011820.a01.pub2 | year = 2001 | mode = cs1}}</ref> They are chemical intermediates often used to make surfactants and as crosslinkers ("hardeners") for epoxy resins.<ref name=lawr>{{cite book |first=Stephen A. |last=Lawrence |title=Amines: synthesis, properties and applications |url=https://books.google.com/books?id=35xwBwjhe2MC&pg=PA64 |year=2004 |publisher=Cambridge University Press |isbn=978-0-521-78284-5 |page=64}} </ref> Some members of this class include: * Ethylenediamine, first member of this series. It is a chelating ligand by itself, and it is a precursor to the popular metal sequestrant, EDTA (ethylenediaminetetraacetic acid). Permethylated, ethylenediamine yields tetramethylethylenediamine (TMEDA) that has a very high affinity for lithium ions.<ref name=EROS>{{cite encyclopedia |last1=Haynes |first1=R. K. |last2=Vonwiller |first2=S. C. |last3=Luderer |first3=M. R. | title = ''N'',''N'',''N''′,''N''′-Tetramethylethylenediamine | encyclopedia = Encyclopedia of Reagents for Organic Synthesis | editor-last = Paquette |editor-first=L. | year = 2006 | publisher = Wiley | doi = 10.1002/047084289X.rt064.pub2 |chapter=N,N,N′,N′-Tetramethylethylenediamine |isbn=0-471-93623-5}}</ref> *Tris(2-aminoethyl)amine ({{chem2|N(CH2CH2NH2)3}}) is a branched polyamine that is a minor side product of the polyethyleneamine process. A related tripodal polyamine is 1,1,1-tris(aminomethyl)ethane. These are chelating ligands. *Polyethylenimine is a polymer derived from aziridine.
Other synthetic polyamines include 1,3,5-triazinane (not to be confused with 1,3,5-triazine) and N-substituted analogs. The methylene ({{chem2|\sCH2}}) linkages are derived from formaldehyde. The reaction product of monoethanolamine and formaldehyde is known industrially as "MEA triazine" (it is actually a triazinane), and it serves as a water-soluble hydrogen sulfide scavenger.<ref>{{cite conference | title = Fresh Insight into the H2S Scavenging Mechanism of MEA-Triazine vs. MMA-Triazine | author1 = G. N. Taylor | author2 = J. J. Wylde | author3 = T. Müller | author4 = J Murison | author5 = F. Schneider | conference = SPE International Conference on Oilfield Chemistry | location = Montgomery, Texas | year = 2017 | number = SPE-184529-MS | doi = 10.2118/184529-MS}}</ref> Hexamethylenetetramine (hexamine) is another product of formaldehyde and ammonia that has various uses in industry. Domestically, it is used as a solid camping fuel. In the laboratory, it reacts with alkyl halides to selectively prepare primary amines in the Delépine reaction.
<gallery caption="Synthetic polyamines" widths="160px" heights="110px"> File:Diethylene triamine.png|Diethylenetriamine File:N1,N1'-(ethane-1,2-diyl)bis(ethane-1,2-diamine) 200.svg|triethylenetetramine File:Tris(2-aminoethyl)amine.svg|Tris(2-aminoethyl)amine File:1,1,1-Tris(aminomethyl)ethane.svg|1,1,1-Tris(aminomethyl)ethane File:Branched PEI.png|Subunit of polyethylenimine File:Hexamine.svg|Hexamethylenetetramine with its adamantane-type structure File:2,32-tet.svg|1,4,8,11-Tetraazaundecane </gallery>
===Polyazamacrocycles=== <gallery caption="Synthetic polyazamacrocycles" widths="160px" heights="110px"> File:1,4,7-triazacyclononane.svg|1,4,7-Triazacyclononane File:Cyclen.svg|Cyclen File:Cyclam.png|cyclam </gallery> Macrocyclic polyamines are analogous to crown ethers. They are employed as ligands in coordination chemistry. Examples include porphyrins, cyclen ({{chem2|(CH2CH2NH)4}}), and the related cyclam. Triazamacrocycles include triazacyclononane. Pentaaza and hexaaza rings are also known, e.g., hexaaza-18-crown-6.
==See also== *Polyamine oxidase *Polyamines in plant stress *Polyamine-modulated factor 1 *Aminopolycarboxylic acids
==References== {{reflist}}
==External links== *[https://web.archive.org/web/20130420091712/http://www4.lu.se/cell-proliferation-group/research/the-role-of-the-polyamines-in-cell-cycle-control-and-program Polyamines in cell cycle proliferation and cell death] *{{cite book |first=Pekka |last=Kilpeläinen |title=Expression and regulation in rat brain and in transgenic mice |publisher=Department of Biochemistry, University of Oulu |date=2002 |isbn=951-42-6631-5 |hdl=10024/37387 |url=https://oulurepo.oulu.fi/handle/10024/37387}} Extensive review of literature through 2001 on polyamine structure, properties, metabolism in mammals, and physiological and pathophysiological roles (See article Table of Contents)
{{Plant_hormones}} {{Authority control}}
Category:Polyamines Category:Plant hormones