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2,6-Diaminopurine

October 21, 2023

2,6-diaminopurine (2,6-DAP, also known as 2-aminoadenine) is a compound once used in the treatment of leukemia.[1] As the Z base, it is found instead of adenine (A) in the genetic material of some bacteriophage viruses.[2]

2,6-Diaminopurine
Names
IUPAC name
7H-purine-2,6-diamine
Other names
2-aminoadenine; 2,6-DAP
Identifiers
  • 1904-98-9 Y
3D model (JSmol)
  • Interactive image
ChEMBL
  • ChEMBL388596 Y=
ChemSpider
  • 28738 Y
ECHA InfoCard 100.016.006
  • 30976
UNII
  • 49P95BAU4Z Y
  • DTXSID0062052
  • InChI=1S/C5H6N6/c6-3-2-4(9-1-8-2)11-5(7)10-3/h1H,(H5,6,7,8,9,10,11) Y=
    Key: MSSXOMSJDRHRMC-UHFFFAOYSA-N Y=
  • InChI=1S/C5H6N6/c6-3-2-4(9-1-8-2)11-5(7)10-3/h1H,(H5,6,7,8,9,10,11)
  • c1[nH]c2c(nc(nc2n1)N)N
Properties
C5H6N6
Molar mass 150.145 g·mol−1
Appearance White to yellow crystalline powder
Density 1.743 g/cm3
Melting point 117 to 122 °C (243 to 252 °F; 390 to 395 K)
2.38 g/L at 20 °C
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
N (what is YN ?)

In August 2011, a report, based on NASA studies with meteorites found on Earth, was published suggesting 2,6-diaminopurine and related organic molecules, including the DNA and RNA components adenine and guanine, may have been formed extraterrestrially in outer space.[3][4][5]

In viruses Edit

Main article: nucleic acid analogues
 
DiampurineT DNA base pair

In cyanophage S-2L (Siphoviridae), diaminopurine is used instead of adenine (host evasion).[6] Diaminopurine base (Z) pairs perfectly with thymine (T) as it is identical to adenine (A) but has an amine group at position 2 forming 3 intermolecular hydrogen bonds, eliminating the major difference between the two types of basepairs (weak:A-T and strong:C-G). This improved stability affects protein-binding interactions that rely on those differences.

Four papers published April 2021 further describes the use and production of the Z-base. It is now known that:[7]

  • The S-2L phage avoids incorporating A bases in the genome by hydrolyzing dATP (DatZ enzyme);[8]
  • The Z base is produced by a pathway involving DUF550 (MazZ) and PurZ in S-2L and Vibrio phage PhiVC8;[9]
  • The PrimPol/AEP DNA polymerase responsible for handling the Z base occurs in the same gene cluster as the three aforementioned enzymes;[10]
  • The Z base is quite widespread in both Siphoviridae and Podoviridae, based on the occurrence of the said gene cluster.[11]

In August 2021, it was shown that DatZ, MazZ and PurZ are sufficient to replace some occurrence of A by Z in the bacterial genome of E. coli; expression of this system is toxic to the cell. The structures of MazZ (subtype 2) and PurZ are also determined, showing a possible link between PurZ and archaeal versions of PurA.[12]

Biosynthesis Edit

2-aminoadenine is produced in two steps. The enzyme MazZ (homologous to MazG, EC 3.6.1.8) first performs:[12]

dGTP + H2O = dGMP + diphosphate

The enzyme PurZ (homologous to PurA, EC 6.3.4.4) then performs:[9]

(d)ATP + dGMP + L-aspartate = (d)ADP + phosphate + 2-aminodeoxyadenylosuccinate (dSMP)

The resulting dSMP is processed by host enzymes analogously to adenylosuccinate to produce dZTP.

In cellular life Edit

2,6-DAP was used to treat leukemia since as early as 1951.[13] It is known to arrest progression of cell cycle in mouse leukemia cells by 1989.[14] Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase (APRT) function,[15] a process shared with E. coli.[16]

DAP derivatives are in vitro antivirals useful against pseudorabies virus, a economically important livestock disease.[17] This base, in its free form, is able to correct UGA nonsense mutations by encouraging translational readthrough, through the inhibition of FTSJ1.[18]

Bioengineering Edit

In bioengineering, anti-miRNA oligonucleotides (specifically, the serinol nucleic acid [SNA] type) incorporating base Z instead of A show enhanced binding to RNA.[19]

DAP is used similar to other nuclear acid analogues in the investigation of enzyme structures and mechanisms.[20]

References Edit

  1. ^ "George H. Hitchings". nobelprize.org.
  2. ^ "Some viruses thwart bacterial defenses with a unique genetic alphabet". 5 May 2021.
  3. ^ Callahan, M.P.; Smith, K.E.; Cleaves, H.J.; Ruzica, J.; Stern, J.C.; Glavin, D.P.; House, C.H.; Dworkin, J.P. (11 August 2011). "Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases". Proceedings of the National Academy of Sciences. PNAS. 108 (34): 13995–13998. Bibcode:2011PNAS..10813995C. doi:10.1073/pnas.1106493108. PMC 3161613. PMID 21836052.
  4. ^ Steigerwald, John (8 August 2011). "NASA Researchers: DNA Building Blocks Can Be Made in Space". NASA. Retrieved 2011-08-10.
  5. ^ ScienceDaily Staff (9 August 2011). "DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests". ScienceDaily. Retrieved 2011-08-09.
  6. ^ Kirnos MD, Khudyakov IY, Alexandrushkina NI, Vanyushin BF. 2-aminoadenine is an adenine substituting for a base in S-2L cyanophage DNA. Nature. 1977 Nov 24;270(5635):369–70.
  7. ^ Jacinta Bowler: Some Viruses Have a Completely Different Genome to The Rest of Life on Earth, on: sciencealert, 4 MAY 2021
  8. ^ Czernecki, Dariusz; Legrand, Pierre; Tekpinar, Mustafa; Rosario, Sandrine; Kaminski, Pierre-Alexandre; Delarue, Marc (2021-04-23). "How cyanophage S-2L rejects adenine and incorporates 2-aminoadenine to saturate hydrogen bonding in its DNA". Nature Communications. 12 (1): 2420. Bibcode:2021NatCo..12.2420C. doi:10.1038/s41467-021-22626-x. ISSN 2041-1723. PMC 8065100. PMID 33893297.
  9. ^ a b Sleiman, Dona; Garcia, Pierre Simon; Lagune, Marion; Loc’h, Jerome; Haouz, Ahmed; Taib, Najwa; Röthlisberger, Pascal; Gribaldo, Simonetta; Marlière, Philippe; Kaminski, Pierre Alexandre (30 April 2021). "A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes". Science. 372 (6541): 516–520. Bibcode:2021Sci...372..516S. doi:10.1126/science.abe6494. PMID 33926955. S2CID 233448787.
  10. ^ Pezo, Valerie; Jaziri, Faten; Bourguignon, Pierre-Yves; Louis, Dominique; Jacobs-Sera, Deborah; Rozenski, Jef; Pochet, Sylvie; Herdewijn, Piet; Hatfull, Graham F.; Kaminski, Pierre-Alexandre; Marliere, Philippe (30 April 2021). "Noncanonical DNA polymerization by aminoadenine-based siphoviruses". Science. 372 (6541): 520–524. Bibcode:2021Sci...372..520P. doi:10.1126/science.abe6542. PMID 33926956. S2CID 233448788.
  11. ^ Zhou, Yan; Su, Xuexia; Wei, Yifeng; Cheng, Yu; Guo, Yu; Khudyakov, Ivan; Liu, Fuli; He, Ping; Song, Zhangyue; Li, Zhi; Gao, Yan; Ang, Ee Lui; Zhao, Huimin; Zhang, Yan; Zhao, Suwen (30 April 2021). "A widespread pathway for substitution of adenine by diaminopurine in phage genomes". Science. 372 (6541): 512–516. Bibcode:2021Sci...372..512Z. doi:10.1126/science.abe4882. PMID 33926954. S2CID 233448821.
  12. ^ a b Czernecki, Dariusz; Bonhomme, Frédéric; Kaminski, Pierre-Alexandre; Delarue, Marc (2021-08-05). "Characterization of a triad of genes in cyanophage S-2L sufficient to replace adenine by 2-aminoadenine in bacterial DNA". Nature Communications. 12 (1): 4710. Bibcode:2021NatCo..12.4710C. doi:10.1038/s41467-021-25064-x. ISSN 2041-1723. PMC 8342488. PMID 34354070.
  13. ^ BURCHENAL, JH; KARNOFSKY, DA; KINGSLEY-PILLERS, EM; SOUTHAM, CM; MYERS, WP; ESCHER, GC; CRAVER, LF; DARGEON, HW; RHOADS, CP (May 1951). "The effects of the folic acid antagonists and 2,6-diaminopurine on neoplastic disease, with special reference to acute leukemia". Cancer. 4 (3): 549–69. doi:10.1002/1097-0142(195105)4:3<549::aid-cncr2820040308>3.0.co;2-j. PMID 14839611. S2CID 31262125.
  14. ^ Weckbecker, G; Cory, JG (1989). "Metabolic activation of 2,6-diaminopurine and 2,6-diaminopurine-2'-deoxyriboside to antitumor agents". Advances in Enzyme Regulation. 28: 125–44. doi:10.1016/0065-2571(89)90068-x. PMID 2624171.
  15. ^ Shao, C; Deng, L; Henegariu, O; Liang, L; Stambrook, PJ; Tischfield, JA (20 June 2000). "Chromosome instability contributes to loss of heterozygosity in mice lacking p53". Proceedings of the National Academy of Sciences of the United States of America. 97 (13): 7405–10. Bibcode:2000PNAS...97.7405S. doi:10.1073/pnas.97.13.7405. PMC 16558. PMID 10861008.
  16. ^ Kocharian, ShM; Chukanova, TI; Sukhodolets, VV (1977). "[Mutations of resistance to 2,6-diaminopurine and 6-methylpurine that affect adenine phosphoribosyltransferase in Escherichia coli K-12]". Genetika. 13 (10): 1821–30. PMID 348574.
  17. ^ Zouharova, D; Lipenska, I; Fojtikova, M; Kulich, P; Neca, J; Slany, M; Kovarcik, K; Turanek-Knotigova, P; Hubatka, F; Celechovska, H; Masek, J; Koudelka, S; Prochazka, L; Eyer, L; Plockova, J; Bartheldyova, E; Miller, AD; Ruzek, D; Raska, M; Janeba, Z; Turanek, J (29 February 2016). "Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1)". Veterinary Microbiology. 184: 84–93. doi:10.1016/j.vetmic.2016.01.010. PMID 26854349.
  18. ^ Trzaska, C; Amand, S; Bailly, C; Leroy, C; Marchand, V; Duvernois-Berthet, E; Saliou, JM; Benhabiles, H; Werkmeister, E; Chassat, T; Guilbert, R; Hannebique, D; Mouray, A; Copin, MC; Moreau, PA; Adriaenssens, E; Kulozik, A; Westhof, E; Tulasne, D; Motorin, Y; Rebuffat, S; Lejeune, F (20 March 2020). "2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations". Nature Communications. 11 (1): 1509. Bibcode:2020NatCo..11.1509T. doi:10.1038/s41467-020-15140-z. PMC 7083880. PMID 32198346.
  19. ^ Kamiya, Y; Donoshita, Y; Kamimoto, H; Murayama, K; Ariyoshi, J; Asanuma, H (5 October 2017). "Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA Performance". ChemBioChem. 18 (19): 1917–1922. doi:10.1002/cbic.201700272. PMID 28748559. S2CID 35619213.
  20. ^ Bailly, C (1 October 1998). "The use of diaminopurine to investigate structural properties of nucleic acids and molecular recognition between ligands and DNA". Nucleic Acids Research. 26 (19): 4309–4314. doi:10.1093/nar/26.19.4309. PMC 147870. PMID 9742229.

October 21, 2023
diaminopurine, diaminopurine, also, known, aminoadenine, compound, once, used, treatment, leukemia, base, found, instead, adenine, genetic, material, some, bacteriophage, viruses, namesiupac, name, purine, diamineother, names, aminoadenine, dapidentifierscas, . 2 6 diaminopurine 2 6 DAP also known as 2 aminoadenine is a compound once used in the treatment of leukemia 1 As the Z base it is found instead of adenine A in the genetic material of some bacteriophage viruses 2 2 6 Diaminopurine NamesIUPAC name 7H purine 2 6 diamineOther names 2 aminoadenine 2 6 DAPIdentifiersCAS Number 1904 98 9 Y3D model JSmol Interactive imageChEMBL ChEMBL388596 Y ChemSpider 28738 YECHA InfoCard 100 016 006PubChem CID 30976UNII 49P95BAU4Z YCompTox Dashboard EPA DTXSID0062052InChI InChI 1S C5H6N6 c6 3 2 4 9 1 8 2 11 5 7 10 3 h1H H5 6 7 8 9 10 11 Y Key MSSXOMSJDRHRMC UHFFFAOYSA N Y InChI 1S C5H6N6 c6 3 2 4 9 1 8 2 11 5 7 10 3 h1H H5 6 7 8 9 10 11 SMILES c1 nH c2c nc nc2n1 N NPropertiesChemical formula C 5H 6N 6Molar mass 150 145 g mol 1Appearance White to yellow crystalline powderDensity 1 743 g cm3Melting point 117 to 122 C 243 to 252 F 390 to 395 K Solubility in water 2 38 g L at 20 CExcept where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa N what is Y N Infobox references In August 2011 a report based on NASA studies with meteorites found on Earth was published suggesting 2 6 diaminopurine and related organic molecules including the DNA and RNA components adenine and guanine may have been formed extraterrestrially in outer space 3 4 5 Contents 1 In viruses 2 Biosynthesis 3 In cellular life 4 Bioengineering 5 ReferencesIn viruses EditMain article nucleic acid analogues nbsp DiampurineT DNA base pairIn cyanophage S 2L Siphoviridae diaminopurine is used instead of adenine host evasion 6 Diaminopurine base Z pairs perfectly with thymine T as it is identical to adenine A but has an amine group at position 2 forming 3 intermolecular hydrogen bonds eliminating the major difference between the two types of basepairs weak A T and strong C G This improved stability affects protein binding interactions that rely on those differences Four papers published April 2021 further describes the use and production of the Z base It is now known that 7 The S 2L phage avoids incorporating A bases in the genome by hydrolyzing dATP DatZ enzyme 8 The Z base is produced by a pathway involving DUF550 MazZ and PurZ in S 2L and Vibrio phage PhiVC8 9 The PrimPol AEP DNA polymerase responsible for handling the Z base occurs in the same gene cluster as the three aforementioned enzymes 10 The Z base is quite widespread in both Siphoviridae and Podoviridae based on the occurrence of the said gene cluster 11 In August 2021 it was shown that DatZ MazZ and PurZ are sufficient to replace some occurrence of A by Z in the bacterial genome of E coli expression of this system is toxic to the cell The structures of MazZ subtype 2 and PurZ are also determined showing a possible link between PurZ and archaeal versions of PurA 12 Biosynthesis Edit2 aminoadenine is produced in two steps The enzyme MazZ homologous to MazG EC 3 6 1 8 first performs 12 dGTP H2O dGMP diphosphateThe enzyme PurZ homologous to PurA EC 6 3 4 4 then performs 9 d ATP dGMP L aspartate d ADP phosphate 2 aminodeoxyadenylosuccinate dSMP The resulting dSMP is processed by host enzymes analogously to adenylosuccinate to produce dZTP In cellular life EditThis article is missing information about results of the altered H bond strength in DNA and RNA Please expand the article to include this information Further details may exist on the talk page October 2021 2 6 DAP was used to treat leukemia since as early as 1951 13 It is known to arrest progression of cell cycle in mouse leukemia cells by 1989 14 Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase APRT function 15 a process shared with E coli 16 DAP derivatives are in vitro antivirals useful against pseudorabies virus a economically important livestock disease 17 This base in its free form is able to correct UGA nonsense mutations by encouraging translational readthrough through the inhibition of FTSJ1 18 Bioengineering EditIn bioengineering anti miRNA oligonucleotides specifically the serinol nucleic acid SNA type incorporating base Z instead of A show enhanced binding to RNA 19 DAP is used similar to other nuclear acid analogues in the investigation of enzyme structures and mechanisms 20 References Edit George H Hitchings nobelprize org Some viruses thwart bacterial defenses with a unique genetic alphabet 5 May 2021 Callahan M P Smith K E Cleaves H J Ruzica J Stern J C Glavin D P House C H Dworkin J P 11 August 2011 Carbonaceous meteorites contain a wide range of extraterrestrial nucleobases Proceedings of the National Academy of Sciences PNAS 108 34 13995 13998 Bibcode 2011PNAS 10813995C doi 10 1073 pnas 1106493108 PMC 3161613 PMID 21836052 Steigerwald John 8 August 2011 NASA Researchers DNA Building Blocks Can Be Made in Space NASA Retrieved 2011 08 10 ScienceDaily Staff 9 August 2011 DNA Building Blocks Can Be Made in Space NASA Evidence Suggests ScienceDaily Retrieved 2011 08 09 Kirnos MD Khudyakov IY Alexandrushkina NI Vanyushin BF 2 aminoadenine is an adenine substituting for a base in S 2L cyanophage DNA Nature 1977 Nov 24 270 5635 369 70 Jacinta Bowler Some Viruses Have a Completely Different Genome to The Rest of Life on Earth on sciencealert 4 MAY 2021 Czernecki Dariusz Legrand Pierre Tekpinar Mustafa Rosario Sandrine Kaminski Pierre Alexandre Delarue Marc 2021 04 23 How cyanophage S 2L rejects adenine and incorporates 2 aminoadenine to saturate hydrogen bonding in its DNA Nature Communications 12 1 2420 Bibcode 2021NatCo 12 2420C doi 10 1038 s41467 021 22626 x ISSN 2041 1723 PMC 8065100 PMID 33893297 a b Sleiman Dona Garcia Pierre Simon Lagune Marion Loc h Jerome Haouz Ahmed Taib Najwa Rothlisberger Pascal Gribaldo Simonetta Marliere Philippe Kaminski Pierre Alexandre 30 April 2021 A third purine biosynthetic pathway encoded by aminoadenine based viral DNA genomes Science 372 6541 516 520 Bibcode 2021Sci 372 516S doi 10 1126 science abe6494 PMID 33926955 S2CID 233448787 Pezo Valerie Jaziri Faten Bourguignon Pierre Yves Louis Dominique Jacobs Sera Deborah Rozenski Jef Pochet Sylvie Herdewijn Piet Hatfull Graham F Kaminski Pierre Alexandre Marliere Philippe 30 April 2021 Noncanonical DNA polymerization by aminoadenine based siphoviruses Science 372 6541 520 524 Bibcode 2021Sci 372 520P doi 10 1126 science abe6542 PMID 33926956 S2CID 233448788 Zhou Yan Su Xuexia Wei Yifeng Cheng Yu Guo Yu Khudyakov Ivan Liu Fuli He Ping Song Zhangyue Li Zhi Gao Yan Ang Ee Lui Zhao Huimin Zhang Yan Zhao Suwen 30 April 2021 A widespread pathway for substitution of adenine by diaminopurine in phage genomes Science 372 6541 512 516 Bibcode 2021Sci 372 512Z doi 10 1126 science abe4882 PMID 33926954 S2CID 233448821 a b Czernecki Dariusz Bonhomme Frederic Kaminski Pierre Alexandre Delarue Marc 2021 08 05 Characterization of a triad of genes in cyanophage S 2L sufficient to replace adenine by 2 aminoadenine in bacterial DNA Nature Communications 12 1 4710 Bibcode 2021NatCo 12 4710C doi 10 1038 s41467 021 25064 x ISSN 2041 1723 PMC 8342488 PMID 34354070 BURCHENAL JH KARNOFSKY DA KINGSLEY PILLERS EM SOUTHAM CM MYERS WP ESCHER GC CRAVER LF DARGEON HW RHOADS CP May 1951 The effects of the folic acid antagonists and 2 6 diaminopurine on neoplastic disease with special reference to acute leukemia Cancer 4 3 549 69 doi 10 1002 1097 0142 195105 4 3 lt 549 aid cncr2820040308 gt 3 0 co 2 j PMID 14839611 S2CID 31262125 Weckbecker G Cory JG 1989 Metabolic activation of 2 6 diaminopurine and 2 6 diaminopurine 2 deoxyriboside to antitumor agents Advances in Enzyme Regulation 28 125 44 doi 10 1016 0065 2571 89 90068 x PMID 2624171 Shao C Deng L Henegariu O Liang L Stambrook PJ Tischfield JA 20 June 2000 Chromosome instability contributes to loss of heterozygosity in mice lacking p53 Proceedings of the National Academy of Sciences of the United States of America 97 13 7405 10 Bibcode 2000PNAS 97 7405S doi 10 1073 pnas 97 13 7405 PMC 16558 PMID 10861008 Kocharian ShM Chukanova TI Sukhodolets VV 1977 Mutations of resistance to 2 6 diaminopurine and 6 methylpurine that affect adenine phosphoribosyltransferase in Escherichia coli K 12 Genetika 13 10 1821 30 PMID 348574 Zouharova D Lipenska I Fojtikova M Kulich P Neca J Slany M Kovarcik K Turanek Knotigova P Hubatka F Celechovska H Masek J Koudelka S Prochazka L Eyer L Plockova J Bartheldyova E Miller AD Ruzek D Raska M Janeba Z Turanek J 29 February 2016 Antiviral activities of 2 6 diaminopurine based acyclic nucleoside phosphonates against herpesviruses In vitro study results with pseudorabies virus PrV SuHV 1 Veterinary Microbiology 184 84 93 doi 10 1016 j vetmic 2016 01 010 PMID 26854349 Trzaska C Amand S Bailly C Leroy C Marchand V Duvernois Berthet E Saliou JM Benhabiles H Werkmeister E Chassat T Guilbert R Hannebique D Mouray A Copin MC Moreau PA Adriaenssens E Kulozik A Westhof E Tulasne D Motorin Y Rebuffat S Lejeune F 20 March 2020 2 6 Diaminopurine as a highly potent corrector of UGA nonsense mutations Nature Communications 11 1 1509 Bibcode 2020NatCo 11 1509T doi 10 1038 s41467 020 15140 z PMC 7083880 PMID 32198346 Kamiya Y Donoshita Y Kamimoto H Murayama K Ariyoshi J Asanuma H 5 October 2017 Introduction of 2 6 Diaminopurines into Serinol Nucleic Acid Improves Anti miRNA Performance ChemBioChem 18 19 1917 1922 doi 10 1002 cbic 201700272 PMID 28748559 S2CID 35619213 Bailly C 1 October 1998 The use of diaminopurine to investigate structural properties of nucleic acids and molecular recognition between ligands and DNA Nucleic Acids Research 26 19 4309 4314 doi 10 1093 nar 26 19 4309 PMC 147870 PMID 9742229 Retrieved from https en wikipedia org w index php title 2 6 Diaminopurine amp oldid 1171910445, wikipedia, wiki, book, books, library,

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