Polyamine
Apolyamineis anorganic compoundhaving more than twoamino 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.[1]Mostaromaticpolyamines are crystalline solids at room temperature.
Natural polyamines
[edit]Low-molecular-weight linear polyamines are found in all forms of life. The principal examples are the triaminespermidineand the tetraaminespermine.They are structurally and biosynthetically related to the diaminesputrescineandcadaverine.Polyamine metabolism is regulated by the activity of the enzymeornithine decarboxylase(ODC).[2]Polyamines are found in high concentrations in themammalianbrain.[3]
- Natural polyamines
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Synthetic polyamines
[edit]Ethyleneamines are a commercially-important class of synthetic polyamines with ethylene (−CH2CH2−linkages); global production capacity was estimated at 385,000 tonnes in 2001.[4]They are chemical intermediates often used to make surfactants and as crosslinkers forepoxyresins.[5]Some interesting 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 yieldstetramethylethylenediamine(TMEDA) that has a very high affinity for lithium ions.[6]
- Macrocyclicpolyamines analogous tocrown ethers:1,4,7-triazacyclononane((NHCH2CH2)3) andcyclen((NHCH2CH2)4). A related tetraaza macrocycle iscyclam.
- Tris(2-aminoethyl)amine(N(CH2CH2NH2)3) is a branched polyamine that is a minor side product of thepolyethyleneamineprocess. A related tripodal polyamine is1,1,1-tris(aminomethyl)ethane.These are interesting chelating ligands.
- Polyethylenimineis apolymerderived fromaziridine.
Other synthetic polyamines include1,3,5-triazinane(not to be confused with1,3,5-triazine) and N-substituted analogs. The methylene (−CH2) linkages are derived fromformaldehyde.The reaction product of monoethanolamine and formaldehyde is known industrially as "MEA triazine" (it is actually a triazinane), and it serves as a water-solublehydrogen sulfidescavenger.[7]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 withalkyl halidesto selectively prepare primary amines in theDelépine reaction.
- Synthetic polyamines
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Subunit ofpolyethylenimine -
Hexamethylenetetraminewith itsadamantane-type structure
Biological function
[edit]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 toDNA,and, in structure, they represent compounds with cations that are found atregularly spaced intervals(in contrast toMg2+
orCa2+
,which are point charges). They have also been found to act as promoters of programmed ribosomal frameshifting during translation.[8]
Inhibition of polyamine biosynthesis retards or stopscell growth.The provision of exogenous polyamines restores the growth of these cells. Most eukaryotic cells express apolyamine-transporting ATPaseon theircell membranethat 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.[9]
Polyamines are also modulators of a variety ofion channels,includingNMDA receptorsandAMPA receptors.They blockinward-rectifier potassium channelsso 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-producingE. coliunder stress conditions.[10]
Polyamines can enhance the permeability of theblood–brain barrier.[11]
They are involved in modulatingsenescenceof organs in plants and are therefore considered as aplant hormone.[12]In addition, they are directly involved in regulation of programmed cell death.[13]
Homology-directed DNA repair
[edit]Polyamines promotehomologous recombination(HR)-mediateddouble-strand break (DSB) repair.[14]Polyamines enhance the DNA strand exchange activity ofRAD51recombinase.Depletion of polyamines sensitizes cells togenotoxic substancessuch asionizing radiationandultravioletradiation. 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.[14]Polyamines appear to have an evolutionarily conserved role in regulating recombinase activity.
Biosynthesis of spermidine, spermine, thermospermine
[edit]
Spermidineis synthesized from putrescine, using an aminopropyl group from decarboxylatedS-adenosyl-L-methionine(SAM),S-Adenosylmethioninamine.The reaction is catalyzed byspermidine synthase.[15]
Spermineis synthesized from the reaction of spermidine with SAM in the presence of the enzymespermine 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.[15]
Thermospermine (NH2−(CH2)3−NH−(CH2)3−NH−(CH2)4−NH2) is a structuralisomerof spermine and a novel type of plant growth regulator. It is produced from spermidine by the action ofthermospermine synthase,which is encoded by a gene named ACAULIS5 (ACL5).[16]
Polyamine analogues
[edit]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 incancer therapy.Polyamine analogues upregulatep53in a cell leading to restriction of proliferation andapoptosis.[17]It also decreases the expression of estrogen receptor alpha in ER-positive breast cancer.[18]
See also
[edit]References
[edit]- ^Eller, Karsten; Henkes, Erhard; Rossbacher, Roland; Höke, Hartmut (2005). "Amines, Aliphatic".Ullmann's Encyclopedia of Industrial Chemistry.Weinheim: Wiley-VCH.doi:10.1002/14356007.a02_001.ISBN978-3527306732.
- ^Pegg, AE; McCann, PP (1982). "Polyamine metabolism and function".American Journal of Physiology.243(5): 212–221.doi:10.1152/ajpcell.1982.243.5.C212.PMID6814260.S2CID21063248.
- ^Seiler, N. (1982)."Polyamines".In Lajtha, A. (ed.).Chemical and Cellular Architecture.Handbook of Neurochemistry. Vol. 1 (2nd ed.). Springer. pp. 223–255.doi:10.1007/978-1-4757-0614-7_9.ISBN978-1-4757-0614-7.
- ^Srivasan Sridhar; Richard G. Carter (2001). "Diamines and Higher Amines, Aliphatic".Kirk-Othmer Encyclopedia of Chemical Technology.New York: John Wiley.doi:10.1002/0471238961.0409011303011820.a01.pub2.ISBN9780471238966.
- ^Lawrence, Stephen A. (2004).Amines: synthesis, properties and applications.Cambridge University Press. p. 64.ISBN978-0-521-78284-5.
- ^Haynes, R. K.; Vonwiller, S. C.; Luderer, M. R. (2006). "N,N,N′,N′-Tetramethylethylenediamine". In Paquette, L. (ed.).N,N,N′,N′-Tetramethylethylenediamine.Encyclopedia of Reagents for Organic Synthesis.Wiley.doi:10.1002/047084289X.rt064.pub2.ISBN0-471-93623-5.
- ^G. N. Taylor; J. J. Wylde; T. Müller; J Murison; F. Schneider (2017).Fresh Insight into the H2S Scavenging Mechanism of MEA-Triazine vs. MMA-Triazine.SPE International Conference on Oilfield Chemistry. Montgomery, Texas.doi:10.2118/184529-MS.
- ^Rato C; Amirova S.R; Bates D.G; Stansfield I; Wallace H.M (June 2011)."Translational recoding as a feedback controller: systems approaches reveal polyamine-specific effects on the antizyme ribosomal frameshift".Nucleic Acids Res.39(11): 4587–97.doi:10.1093/nar/gkq1349.PMC3113565.PMID21303766.
- ^Wang C, Delcros JG, Cannon L, Konate F, Carias H, Biggerstaff J, Gardner RA, Phanstiel IV O (November 2003). "Defining the molecular requirements for the selective delivery of polyamine conjugates into cells containing active polyamine transporters".J Med Chem.46(24): 5129–38.doi:10.1021/jm030223a.PMID14613316.
- ^Yi-Hsuan Pan; Chen-Chung Liao (May 2006)."The critical roles of polyamines regulating ColE7 production and restricting ColE7 uptake of the colicin-producing Escherichia coli".J. Biol. Chem.281(19): 13083–91.doi:10.1074/jbc.M511365200.PMID16549429.
- ^Zhang L, Lee HK, Pruess TH, White HS, Bulaj G (March 2009)."Synthesis and applications of polyamine amino acid residues: improving the bioactivity of an analgesic neuropeptide, neurotensin".J. Med. Chem.52(6): 1514–7.doi:10.1021/jm801481y.PMC2694617.PMID19236044.
- ^Pandey S, Ranade SA, Nagar PK, Kumar N (September 2000). "Role of polyamines and ethylene as modulators of plant senescence".J. Biosci.25(3): 291–9.doi:10.1007/BF02703938.PMID11022232.S2CID21925829.
- ^Moschou, PN; Roubelakis-Angelakis, KA (Nov 11, 2013)."Polyamines and programmed cell death".Journal of Experimental Botany.65(5): 1285–96.doi:10.1093/jxb/ert373.PMID24218329.
- ^abLee CY, Su GC, Huang WY, Ko MY, Yeh HY, Chang GD, Lin SJ, Chi P (January 2019)."Promotion of homology-directed DNA repair by polyamines".Nat Commun.10(1): 65.Bibcode:2019NatCo..10...65L.doi:10.1038/s41467-018-08011-1.PMC6325121.PMID30622262.
- ^abPál M, Szalai G, Janda T (2015)."Speculation: Polyamines are important in abiotic stress signaling"(PDF).Plant Science.237:16–23.Bibcode:2015PlnSc.237...16P.doi:10.1016/j.plantsci.2015.05.003.PMID26089148.
- ^Takano, A; Kakehi, J; Takahashi, T (April 2012)."Thermospermine is not a minor polyamine in the plant kingdom".Plant Cell Physiol.53(4): 606–16.doi:10.1093/pcp/pcs019.PMID22366038.
- ^Huang, Yi; Pledgie, Allison; Rubin, Ethel; Marton, Laurence J.; Woster, Patrick M.; Sukumar, Saraswati; Casero, Robert A.; Davidson, Nancy E. (September 2005)."Role of p53/p21(Waf1/Cip1) in the regulation of polyamine analogue-induced growth inhibition and cell death in human breast cancer cells".Cancer Biology & Therapy.4(9): 1006–13.doi:10.4161/cbt.4.9.1970.PMC3639297.PMID16131835.
- ^Huang, Y; Keen, JC; Pledgie, A; Marton, LJ; Zhu, T; Sukumar, S; Park, BH; Blair, B; Brenner, K; Casero, RA Jr; Davidson, NE (2006)."Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells".J Biol Chem.281(28): 19055–63.doi:10.1074/jbc.M600910200.PMC3623667.PMID16679312.
External links
[edit]- Polyamines in cell cycle proliferation and cell death
- Kilpeläinen, Pekka (2002).Expression and regulation in rat brain and in transgenic mice.Department of Biochemistry, University of Oulu.hdl:10024/37387.ISBN951-42-6631-5.Extensive review of literature through 2001 on polyamine structure, properties, metabolism in mammals, and physiological and pathophysiological roles (See article Table of Contents)
