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Record Information
Version5.0
StatusDetected and Quantified
Creation Date2005-11-16 15:48:42 UTC
Update Date2021-09-14 15:47:20 UTC
HMDB IDHMDB0001211
Secondary Accession Numbers
  • HMDB01211
Metabolite Identification
Common NameDiadenosine tetraphosphate
DescriptionDiadenosine tetraphosphate (AP4A) is a diadenosine polyphosphate. Diadenosine polyphosphates (APnAs, n=3-6) are a family of endogenous vasoactive purine dinucleotides which have been isolated from thrombocytes. APnAs have been demonstrated to be involved in the control of vascular tone as well as the growth of vascular smooth muscle cells and hence, possibly, in atherogenesis. APnAs isolated substances are Ap3A, Ap4A, Ap5A, and Ap6A. APnAs are naturally occurring substances that facilitate tear secretion; they are released from the corneal epithelium, they stimulate tear production and therefore they may be considered as physiological modulators of tear secretion. 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. Great variety of physiological and pathological effects in mammalian cells was found to be associated with alterations of APnAs. APnAs are polyphosphated nucleotidic substances which are found in the CNS and are known to be released in a calcium-dependent manner from storage vesicles in brain synaptosomes. AP5A is a specific adenylate kinase inhibitor in the hippocampus, decreasing the rate of decomposition of ADP and the formation of ATP; a pathway that influences the availability of purines in the central nervous system. AP4A is the only APnA that can induce a considerable increase in [Ca2+] in endothelial cells, indicating that its vasoactive effects are comparable to the known effects of arginine vasopressin, Angiotensin II, and ATP. AP4A is a ubiquitous ApnA is a signal molecule for DNA replication in mammalian cells. AP4A is a primer for oligoadenylate synthesis catalyzed by interferon-inducible 2-5A synthetase. AP4A is an avid inhibitor of eosinophil-derived neurotoxin (EDN). EDN is a catalytically proficient member of the pancreatic ribonuclease superfamily secreted along with other eosinophil granule proteins during innate host defense responses and various eosinophil-related inflammatory and allergic diseases. The ribonucleolytic activity of EDN is central to its antiviral and neurotoxic activities and possibly to other facets of its biological activity. (PMID: 11212966 , 12738682 , 11810214 , 9607303 , 8922753 , 9187362 , 16401072 , 9694344 , 9351706 , 1953194 ).
Structure
Data?1582752184
Synonyms
ValueSource
(PpA)2ChEBI
a(5')P4(5')aChEBI
AppppAChEBI
Bis(5'-adenylyl) diphosphateChEBI
P1,P4-Bis(5'-adenosyl) tetraphosphateChEBI
Bis(5'-adenylyl) diphosphoric acidGenerator
P1,P4-Bis(5'-adenosyl) tetraphosphoric acidGenerator
Diadenosine tetraphosphoric acidGenerator
5',5'''-diadenosine tetraphosphateHMDB
Adenosine 5'-tetraphosphate, 5'-ester with adenosineHMDB
Adenosine-(5')-tetraphospho-(5')-adenosineHMDB
Diadenosine 5',5'''-P1,P4-tetraphosphateHMDB
P1,P4-Di(adenosin-5'-yl)tetraphosphateHMDB
P1,P4-Diadenosine-5'-tetraphosphateHMDB
Ap4aMeSH, HMDB
P(1), P(4)-Diadenosine-5'tetraphosphateMeSH, HMDB
Diadenosine 5',5'''-P(1),P(4)--tetraphosphateMeSH, HMDB
Adenosine(5')tetraphospho(5')adenosineMeSH, HMDB
Bis(5'-adenosyl)tetraphosphateMeSH, HMDB
P1,P4-Bis(5'-adenosyl)tetraphosphoric acidGenerator, HMDB
Diadenosine tetraphosphateMeSH
p(1),p(4)-Bis(5'-adenosyl) tetraphosphoric acidGenerator, HMDB
Chemical FormulaC20H28N10O19P4
Average Molecular Weight836.387
Monoisotopic Molecular Weight836.048264812
IUPAC Name[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy]({[({[(2R,3S,4R,5R)-5-(6-amino-9H-purin-9-yl)-3,4-dihydroxyoxolan-2-yl]methoxy}(hydroxy)phosphoryl)oxy](hydroxy)phosphoryl}oxy)phosphinic acid
Traditional Nameappppa
CAS Registry Number5542-28-9
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
InChI Identifier
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
InChI KeyYOAHKNVSNCMZGQ-XPWFQUROSA-N
Chemical Taxonomy
Description 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.
KingdomOrganic 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
  • Purine ribonucleoside monophosphate
  • Pentose phosphate
  • Pentose-5-phosphate
  • Glycosyl compound
  • N-glycosyl compound
  • 6-aminopurine
  • Monosaccharide phosphate
  • Purine
  • Imidazopyrimidine
  • Monoalkyl phosphate
  • Aminopyrimidine
  • Alkyl phosphate
  • Monosaccharide
  • N-substituted imidazole
  • Organic phosphoric acid derivative
  • Pyrimidine
  • Phosphoric acid ester
  • Imidolactam
  • Tetrahydrofuran
  • Imidazole
  • Azole
  • Heteroaromatic compound
  • Secondary alcohol
  • Azacycle
  • Oxacycle
  • Organoheterocyclic compound
  • Hydrocarbon derivative
  • Alcohol
  • Organonitrogen compound
  • Organooxygen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Amine
  • Primary amine
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effect
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateSolid
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogP-1.475Not Available
Experimental Chromatographic Properties

Experimental Collision Cross Sections

Adduct TypeData SourceCCS Value (Å2)Reference
[M-H]-Not Available236.898http://allccs.zhulab.cn/database/detail?ID=AllCCS00000119
Predicted Molecular Properties
PropertyValueSource
Water Solubility5.59 g/LALOGPS
logP-0.71ALOGPS
logP-9.5ChemAxon
logS-2.2ALOGPS
pKa (Strongest Acidic)0.59ChemAxon
pKa (Strongest Basic)4.28ChemAxon
Physiological Charge-4ChemAxon
Hydrogen Acceptor Count22ChemAxon
Hydrogen Donor Count10ChemAxon
Polar Surface Area433.97 ŲChemAxon
Rotatable Bond Count14ChemAxon
Refractivity166.1 m³·mol⁻¹ChemAxon
Polarizability66.83 ųChemAxon
Number of Rings6ChemAxon
BioavailabilityNoChemAxon
Rule of FiveNoChemAxon
Ghose FilterNoChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
AllCCS[M+H]+243.97132859911
AllCCS[M-H]-242.28432859911
DeepCCS[M-2H]-255.56130932474
DeepCCS[M+Na]+229.69230932474
AllCCS[M+H]+244.032859911
AllCCS[M+H-H2O]+244.132859911
AllCCS[M+NH4]+243.832859911
AllCCS[M+Na]+243.732859911
AllCCS[M-H]-242.332859911
AllCCS[M+Na-2H]-245.132859911
AllCCS[M+HCOO]-248.332859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
Diadenosine tetraphosphateNC1=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=N16227.6Standard polar33892256
Diadenosine tetraphosphateNC1=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=N13870.4Standard non polar33892256
Diadenosine tetraphosphateNC1=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=N16869.3Semi standard non polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
MSMass Spectrum (Electron Ionization)Not Available2022-08-06Not AvailableView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 10V, Positive-QTOFsplash10-000i-0910200030-f62591a77764336369ca2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 20V, Positive-QTOFsplash10-000i-0900000000-f3c88b3e116ab3d6c1b42015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 40V, Positive-QTOFsplash10-000i-0900000000-ed94ad304e91a867ff3b2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 10V, Negative-QTOFsplash10-0019-0700020090-f52e6941bbc750fe0e762015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 20V, Negative-QTOFsplash10-001i-0900010000-dd233557a62d77a1406b2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 40V, Negative-QTOFsplash10-001i-1915110000-741bdaae70092f502b8e2015-09-15Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 10V, Positive-QTOFsplash10-000i-0100000090-0703d63dcb14292454112021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 20V, Positive-QTOFsplash10-000i-0300002090-89e8cc71cfb144d0f8b62021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 40V, Positive-QTOFsplash10-000i-0900101000-4b74d668fd588964dfd62021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 10V, Negative-QTOFsplash10-000i-0000000090-bc4ce7d28b2ff5fc83e92021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 20V, Negative-QTOFsplash10-000i-0201132090-cd2f5d95fa2a2c4f170a2021-09-24Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Diadenosine tetraphosphate 40V, Negative-QTOFsplash10-0a4r-0410920120-5c5c92a5ab82e5e045d22021-09-24Wishart LabView Spectrum

NMR Spectra

Spectrum TypeDescriptionDeposition DateSourceView
Predicted 1D NMR13C NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 100 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 200 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 300 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 400 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 500 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 600 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 700 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 800 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 900 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR13C NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Predicted 1D NMR1H NMR Spectrum (1D, 1000 MHz, D2O, predicted)2021-09-16Wishart LabView Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
Tissue LocationsNot Available
Pathways
Normal Concentrations
Not Available
Abnormal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected and Quantified0.54 +/- 0.31 uMAdult (>18 years old)BothHemodialysis details
Associated Disorders and Diseases
Disease References
Hemodialysis
  1. 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 ]
Associated OMIM IDsNone
DrugBank IDNot Available
Phenol Explorer Compound IDNot Available
FooDB IDFDB022492
KNApSAcK IDNot Available
Chemspider ID20402
KEGG Compound IDC01260
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkAp4A
METLIN IDNot Available
PubChem Compound21706
PDB IDNot Available
ChEBI ID17422
Food Biomarker OntologyNot Available
VMH IDAP4A
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. Jankowski J, Schluter H, Tepel M, Spieker C, Zidek W: Effect of diadenosine polyphosphates on Ca2+ ATPase activity. J Mol Med (Berl). 1997 Sep;75(9):674-7. [PubMed:9351706 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]
  16. 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 ]
  17. 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 ]
  18. 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 ]
  19. 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 ]
  20. 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 ]

Enzymes

General function:
Involved in hydrolase activity
Specific function:
Asymmetrically hydrolyzes Ap4A to yield AMP and ATP. Plays a major role in maintaining homeostasis.
Gene Name:
NUDT2
Uniprot ID:
P50583
Molecular weight:
16829.09
Reactions
Diadenosine tetraphosphate + Water → Adenosine triphosphate + Adenosine monophosphatedetails