Record Information
Version 1.0
Update Date 1/22/2018 11:54:53 AM
Metabolite IDPAMDB000300
Identification
Name: Diadenosine tetraphosphate
Description:Diadenosine tetraphosphate (AP4A) is a diadenosine polyphosphate. APnAs isolated substances are Ap3A, Ap4A, Ap5A, and Ap6A. The APnAs were discovered in the mid-sixties in the course of studies on aminoacyl-tRNA synthetases (aaRS). APnAs have emerged as intracellular and extracellular signalling molecules implicated in the maintenance and regulation of vital cellular functions and become considered as second messengers. It is an intermediate of purine metabolism pathway.
Structure
Thumb
Synonyms:
  • 5',5'''-Diadenosine tetraphosphate
  • 5',5'''-diadenosine tetraphosphoric acid
  • Adenosine 5'-tetraphosphate, 5'-ester with adenosine
  • Adenosine 5'-tetraphosphoric acid, 5'-ester with adenosine
  • Adenosine-(5')-tetraphospho-(5')-adenosine
  • Ap4A
  • Ap4A
  • AppppA
  • Diadenosine 5',5'''-P1,P4-tetraphosphate
  • Diadenosine 5',5'''-P1,P4-tetraphosphoric acid
  • Diadenosine tetraphosphoric acid
  • P(1),P(4)-Bis(5'-adenosyl)tetraphosphate
  • P(1),P(4)-Bis(5'-adenosyl)tetraphosphoric acid
  • P1,P4-bis(5'-adenosyl)tetraphosphate
  • P1,P4-Bis(5'-adenosyl)tetraphosphoric acid
  • P1,P4-Di(adenosin-5'-yl)tetraphosphate
  • P1,P4-Di(adenosin-5'-yl)tetraphosphoric acid
  • P1,P4-Diadenosine-5'-tetraphosphate
  • P1,P4-Diadenosine-5'-tetraphosphoric acid
  • P1,P4-bis(5'-adenosyl)tetraphosphate
Chemical Formula: C20H28N10O19P4
Average Molecular Weight: 836.387
Monoisotopic Molecular Weight: 836.048264812
InChI Key: YOAHKNVSNCMZGQ-XPWFQUROSA-N
InChI:InChI=1S/C20H28N10O19P4/c21-15-9-17(25-3-23-15)29(5-27-9)19-13(33)11(31)7(45-19)1-43-50(35,36)47-52(39,40)49-53(41,42)48-51(37,38)44-2-8-12(32)14(34)20(46-8)30-6-28-10-16(22)24-4-26-18(10)30/h3-8,11-14,19-20,31-34H,1-2H2,(H,35,36)(H,37,38)(H,39,40)(H,41,42)(H2,21,23,25)(H2,22,24,26)/t7-,8-,11-,12-,13-,14-,19-,20-/m1/s1
CAS number: 5542-28-9
IUPAC Name:{[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}({[({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)(hydroxy)phosphoryl]oxy})phosphinic acid
Traditional IUPAC Name: appppa
SMILES:NC1=C2N=CN([C@@H]3O[C@H](COP(O)(=O)OP(O)(=O)OP(O)(=O)OP(O)(=O)OC[C@H]4O[C@H]([C@H](O)[C@@H]4O)N4C=NC5=C(N)N=CN=C45)[C@@H](O)[C@H]3O)C2=NC=N1
Chemical Taxonomy
Taxonomy DescriptionThis compound belongs to the class of organic compounds known as (5'->5')-dinucleotides. These are dinucleotides where the two bases are connected via a (5'->5')-phosphodiester linkage.
Kingdom Organic compounds
Super ClassNucleosides, nucleotides, and analogues
Class (5'->5')-dinucleotides
Sub ClassNot Available
Direct Parent (5'->5')-dinucleotides
Alternative Parents
Substituents
  • (5'->5')-dinucleotide
  • Purine ribonucleoside polyphosphate
  • Purine nucleotide sugar
  • N-glycosyl compound
  • Glycosyl compound
  • Organic pyrophosphate
  • Monosaccharide phosphate
  • 6-aminopurine
  • Purine
  • Imidazopyrimidine
  • Monoalkyl phosphate
  • Aminopyrimidine
  • Imidolactam
  • Alkyl phosphate
  • Pyrimidine
  • Primary aromatic amine
  • Phosphoric acid ester
  • Organic phosphoric acid derivative
  • Organic phosphate
  • N-substituted imidazole
  • Monosaccharide
  • Saccharide
  • Heteroaromatic compound
  • Oxolane
  • Imidazole
  • Azole
  • Secondary alcohol
  • 1,2-diol
  • Oxacycle
  • Azacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Primary amine
  • Organooxygen compound
  • Organonitrogen compound
  • Amine
  • Alcohol
  • Aromatic heteropolycyclic compound
Molecular Framework Aromatic heteropolycyclic compounds
External Descriptors
Physical Properties
State: Solid
Charge:-4
Melting point: Not Available
Experimental Properties:
PropertyValueSource
LogP:-1.475PhysProp
Predicted Properties
PropertyValueSource
Water Solubility5.59 mg/mLALOGPS
logP-0.71ALOGPS
logP-10ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)0.6ChemAxon
pKa (Strongest Basic)5.29ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count22ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area433.97 Å2ChemAxon
Rotatable Bond Count14ChemAxon
Refractivity166.1 m3·mol-1ChemAxon
Polarizability67.57 Å3ChemAxon
Number of Rings6ChemAxon
Bioavailability0ChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleYesChemAxon
MDDR-like RuleYesChemAxon
Biological Properties
Cellular Locations: Cytoplasm
Reactions:
Pathways:
Spectra
Spectra:
Spectrum TypeDescriptionSplash Key
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Positivesplash10-000i-0910200030-f62591a77764336369caView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Positivesplash10-000i-0900000000-f3c88b3e116ab3d6c1b4View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Positivesplash10-000i-0900000000-ed94ad304e91a867ff3bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 10V, Negativesplash10-0019-0700020090-f52e6941bbc750fe0e76View in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 20V, Negativesplash10-001i-0900010000-dd233557a62d77a1406bView in MoNA
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - 40V, Negativesplash10-001i-1915110000-741bdaae70092f502b8eView in MoNA
References
References:
  • Baker MD, Holloway DE, Swaminathan GJ, Acharya KR: Crystal structures of eosinophil-derived neurotoxin (EDN) in complex with the inhibitors 5'-ATP, Ap3A, Ap4A, and Ap5A. Biochemistry. 2006 Jan 17;45(2):416-26. Pubmed: 16401072
  • Chan PJ, Su BC, Tredway DR: Diadenosine tetraphosphate (Ap4A) and triphosphate (Ap3A) signaling of human sperm motility. Arch Androl. 1991 Sep-Oct;27(2):103-8. Pubmed: 1953194
  • de Korte D, Gouwerok CW, Fijnheer R, Pietersz RN, Roos D: Depletion of dense granule nucleotides during storage of human platelets. Thromb Haemost. 1990 Apr 12;63(2):275-8. Pubmed: 2141956
  • Gualix J, Pintor J, Miras-Portugal MT: Characterization of nucleotide transport into rat brain synaptic vesicles. J Neurochem. 1999 Sep;73(3):1098-104. Pubmed: 10461900
  • Hollah P, Hausberg M, Kosch M, Barenbrock M, Letzel M, Schlatter E, Rahn KH: A novel assay for determination of diadenosine polyphosphates in human platelets: studies in normotensive subjects and in patients with essential hypertension. J Hypertens. 2001 Feb;19(2):237-45. Pubmed: 11212966
  • Hourani SM, Bailey SJ, Johnson CR, Tennant JP: Effects of adenosine 5'-triphosphate, uridine 5'-triphosphate, adenosine 5'-tetraphosphate and diadenosine polyphosphates in guinea-pig taenia caeci and rat colon muscularis mucosae. Naunyn Schmiedebergs Arch Pharmacol. 1998 Oct;358(4):464-73. Pubmed: 9826069
  • Hoyle CH: Pharmacological activity of adenine dinucleotides in the periphery: possible receptor classes and transmitter function. Gen Pharmacol. 1990;21(6):827-31. Pubmed: 2279683
  • Jankowski J, Jankowski V, Laufer U, van der Giet M, Henning L, Tepel M, Zidek W, Schluter H: Identification and quantification of diadenosine polyphosphate concentrations in human plasma. Arterioscler Thromb Vasc Biol. 2003 Jul 1;23(7):1231-8. Epub 2003 May 8. Pubmed: 12738682
  • Jankowski J, Schluter H, Tepel M, Spieker C, Zidek W: Effect of diadenosine polyphosphates on Ca2+ ATPase activity. J Mol Med. 1997 Sep;75(9):674-7. Pubmed: 9351706
  • Kanehisa, M., Goto, S., Sato, Y., Furumichi, M., Tanabe, M. (2012). "KEGG for integration and interpretation of large-scale molecular data sets." Nucleic Acids Res 40:D109-D114. Pubmed: 22080510
  • Keseler, I. M., Collado-Vides, J., Santos-Zavaleta, A., Peralta-Gil, M., Gama-Castro, S., Muniz-Rascado, L., Bonavides-Martinez, C., Paley, S., Krummenacker, M., Altman, T., Kaipa, P., Spaulding, A., Pacheco, J., Latendresse, M., Fulcher, C., Sarker, M., Shearer, A. G., Mackie, A., Paulsen, I., Gunsalus, R. P., Karp, P. D. (2011). "EcoCyc: a comprehensive database of Escherichia coli biology." Nucleic Acids Res 39:D583-D590. Pubmed: 21097882
  • Kisselev LL, Justesen J, Wolfson AD, Frolova LY: Diadenosine oligophosphates (Ap(n)A), a novel class of signalling molecules? FEBS Lett. 1998 May 8;427(2):157-63. Pubmed: 9607303
  • Pintor J, Carracedo G, Alonso MC, Bautista A, Peral A: Presence of diadenosine polyphosphates in human tears. Pflugers Arch. 2002 Jan;443(3):432-6. Epub 2001 Aug 23. Pubmed: 11810214
  • Pintor J, King BF, Miras-Portugal MT, Burnstock G: Selectivity and activity of adenine dinucleotides at recombinant P2X2 and P2Y1 purinoceptors. Br J Pharmacol. 1996 Nov;119(5):1006-12. Pubmed: 8922753
  • Pintor J, Puche JA, Gualix J, Hoyle CH, Miras-Portugal MT: Diadenosine polyphosphates evoke Ca2+ transients in guinea-pig brain via receptors distinct from those for ATP. J Physiol. 1997 Oct 15;504 ( Pt 2):327-35. Pubmed: 9365907
  • Pirrone AM, Gambino R, Oddo F, Faraci MT, Luparello G, Giudice G: Sea urchin embryos do not synthesize diadenosinetetraphosphate. Exp Cell Res. 1979 Sep;122(2):419-22. Pubmed: 510412
  • Stachon A, Stegemann H, Hohage H, Rahn KH, Schlatter E: Effects of diadenosine polyphosphates on the intracellular Ca2+ concentration in endothelial cells. Cell Physiol Biochem. 1998;8(4):175-84. Pubmed: 9694344
  • Stiepanow-Trzeciak A, Jankowski M, Angielski S, Szczepanska-Konkel M: P1,P4-diadenosine tetraphosphate (Ap4A) inhibits proximal tubular reabsorption of sodium in rats. Nephron Physiol. 2007;106(1):p13-8. Epub 2007 Apr 2. Pubmed: 17406124
  • Turpaev K, Hartmann R, Kisselev L, Justesen J: Ap3A and Ap4A are primers for oligoadenylate synthesis catalyzed by interferon-inducible 2-5A synthetase. FEBS Lett. 1997 May 19;408(2):177-81. Pubmed: 9187362
  • van der Giet M, Jankowski J, Schluter H, Zidek W, Tepel M: Mediation of the vasoactive properties of diadenosine tetraphosphate via various purinoceptors. J Hypertens. 1998 Dec;16(12 Pt 2):1939-43. Pubmed: 9886880
  • van der Giet M, Khattab M, Borgel J, Schluter H, Zidek W: Differential effects of diadenosine phosphates on purinoceptors in the rat isolated perfused kidney. Br J Pharmacol. 1997 Apr;120(8):1453-60. Pubmed: 9113365
  • Wildman SS, Brown SG, King BF, Burnstock G: Selectivity of diadenosine polyphosphates for rat P2X receptor subunits. Eur J Pharmacol. 1999 Feb 12;367(1):119-23. Pubmed: 10082274
  • Winder, C. L., Dunn, W. B., Schuler, S., Broadhurst, D., Jarvis, R., Stephens, G. M., Goodacre, R. (2008). "Global metabolic profiling of Escherichia coli cultures: an evaluation of methods for quenching and extraction of intracellular metabolites." Anal Chem 80:2939-2948. Pubmed: 18331064
Synthesis Reference: Not Available
Material Safety Data Sheet (MSDS) Not Available
External Links:
ResourceLink
CHEBI ID17422
HMDB IDHMDB01211
Pubchem Compound ID21706
Kegg IDC01260
ChemSpider ID20402
Wikipedia IDNot Available
BioCyc IDADENOSYL-P4
EcoCyc IDADENOSYL-P4
Ligand ExpoB4P