2,6-Diaminopurine

changed changed 2,6-Diaminopurine.svg skin-invert 7H-Purine-2,6-diamine 2-aminoadenine; 2,6-DAP correct chemspider 28738 correct FDA 49P95BAU4Z correct kegg= 1S/C5H6N6/c6-3-2-4(9-1-8-2)11-5(7)10-3/h1H,(H5,6,7,8,9,10,11) correct EBI= 388596 correct chemspider= 1S/C5H6N6/c6-3-2-4(9-1-8-2)11-5(7)10-3/h1H,(H5,6,7,8,9,10,11) correct chemspider= MSSXOMSJDRHRMC-UHFFFAOYSA-N correct CAS 1904-98-9 30976 Nc1nc(N)nc2c1nc[nH]2 5 6 6 White to yellow crystalline powder 1.743 g/cm3 117 to 122 2.38 g/L at 20 °C 2,6-diaminopurine (2,6-DAP, also known as 2-aminoadenine, standard IUPAC symbol n2A IUPAC-IUB Commission on Biochemical Nomenclature 10.1021/bi00822a023 Abbreviations and symbols for nucleic acids, polynucleotides, and their constituents Biochemistry 9 20 4022–4027 1970 https://iupac.qmul.ac.uk/misc/naabb.html#p44 N4.1,N4.4) is a compound once used in the treatment of leukemia. https://www.nobelprize.org/nobel_prizes/medicine/laureates/1988/hitchings-bio.html George H. Hitchings nobelprize.org It is found instead of adenine (A) in the genetic material of some bacteriophage viruses,https://www.sciencenews.org/article/virus-dna-z-bacteriophage-genetic-alphabet-bond-life Some viruses thwart bacterial defenses with a unique genetic alphabet 5 May 2021 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.Callahan M.P. Smith K.E. Cleaves H.J. Ruzica J. Stern J.C. Jennifer Stern 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 108 34 13995–13998 PNAS 10.1073/pnas.1106493108 21836052 3161613 2011PNAS..10813995C free Steigerwald John NASA Researchers: DNA Building Blocks Can Be Made in Space http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html NASA 8 August 2011 2011-08-10 2015-06-23 https://web.archive.org/web/20150623004556/http://www.nasa.gov/topics/solarsystem/features/dna-meteorites.html deadScienceDaily Staff DNA Building Blocks Can Be Made in Space, NASA Evidence Suggests https://www.sciencedaily.com/releases/2011/08/110808220659.htm 9 August 2011 ScienceDaily 2011-08-09 Abbreviations In virology it is referred to as the "Z" base. However, "Z" refers instead to 6-amino-5-nitropyridin-2-one in the Artificially Expanded Genetic Information System (AEGIS), so context is required to differentiate.Kawabe Hinako Thomas Christopher A. Hoshika Shuichi Kim Myong-Jung Kim Myong-Sang Miessner Logan Kaplan Nicholas Craig Jonathan M. Gundlach Jens H. Laszlo Andrew H. Benner Steven A. Marchand Jorge A. Enzymatic synthesis and nanopore sequencing of 12-letter supernumerary DNA Nature Communications 26 October 2023 14 1 6820 10.1038/s41467-023-42406-z free 37884513 10603101 2023NatCo..14.6820K AEGIS refers to this base as "AminoA" instead.Benner SA Hutter D Sismour AM Synthetic biology with artificially expanded genetic information systems. From personalized medicine to extraterrestrial life. Nucleic Acids Research. Supplement 3 1 September 2003 3 125–6 14510412 10.1093/nass/3.1.125 It has also been called the "D" base,Chou FC Kladwang W Kappel K Das R Blind tests of RNA nearest-neighbor energy prediction. Proceedings of the National Academy of Sciences of the United States of America 26 July 2016 113 30 8430–5 10.1073/pnas.1523335113 free 27402765 4968729 2016PNAS..113.8430C Hopfinger MC Kirkpatrick CC Znosko BM Predictions and analyses of RNA nearest neighbor parameters for modified nucleotides. Nucleic Acids Research 18 September 2020 48 16 8901–8913 10.1093/nar/gkaa654 32810273 7498315 but the more common interpretation of "D" is dihydrouridine. IUPAC-IUB Commission on Biochemical Nomenclature 10.1021/bi00822a023 Abbreviations and symbols for nucleic acids, polynucleotides, and their constituents Biochemistry 9 20 4022–4027 1970 In viruses nucleic acid analogues DiampurineT DNA base pair|thumb|left In cyanophage S-2L (Siphoviridae), diaminopurine is used instead of adenine (host evasion).Kirnos MD Khudyakov IY Alexandrushkina NI Vanyushin BF 2-aminoadenine is an adenine substituting for a base in S-2L cyanophage DNA Nature November 1977 270 5635 369–70 413053 10.1038/270369a0 1977Natur.270..369Kcite Q Q34051647 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:Jacinta Bowler https://www.sciencealert.com/some-bacteriophages-have-a-completely-different-genome-to-the-rest-of-life-on-earth Some Viruses Have a Completely Different Genome to The Rest of Life on Earth ScienceAlert 4 May 2021 The S-2L phage avoids incorporating A bases in the genome by hydrolyzing dATP (DatZ enzyme);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 en 12 1 2420 10.1038/s41467-021-22626-x 33893297 8065100 2021NatCo..12.2420C 2041-1723 free The Z base is produced by a pathway involving DUF550 (MazZ) and PurZ in S-2L and Vibrio phage PhiVC8;30 April 2021 372 6541 Science 10.1126/science.abe6494 A third purine biosynthetic pathway encoded by aminoadenine-based viral DNA genomes Dona Sleiman Pierre Simon Garcia Marion Lagune Jerome Loc’h Ahmed Haouz Najwa Taib Pascal Röthlisberger Simonetta Gribaldo Philippe Marlière Pierre Alexandre Kaminski 516–520 33926955 2021Sci...372..516S 233448787 The PrimPol/AEP DNA polymerase responsible for handling the Z base occurs in the same gene cluster as the three aforementioned enzymes;30 April 2021 372 6541 Science 10.1126/science.abe6542 Noncanonical DNA polymerization by aminoadenine-based siphoviruses Valerie Pezo Faten Jaziri Pierre-Yves Bourguignon Dominique Louis Deborah Jacobs-Sera Jef Rozenski Sylvie Pochet Piet Herdewijn Graham F. Hatfull Pierre-Alexandre Kaminski Philippe Marliere 520–524 33926956 2021Sci...372..520P 233448788 The Z base is quite widespread in both Siphoviridae and Podoviridae, based on the occurrence of the said gene cluster.Zhou Yan Su Xuexia Wei Yifeng Yu Cheng Yu Guo Ivan Khudyakov Fuli Liu Ping He Zhangyue Song Zhi Li Yan Gao Ee Lui Ang Huimin Zhao Yan Zhang Suwen Zhao 30 April 2021 372 6541 Science 10.1126/science.abe4882 A widespread pathway for substitution of adenine by diaminopurine in phage genomes 512–516 33926954 2021Sci...372..512Z 233448821 https://www.researchgate.net/publication/351214584 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.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 en 12 1 4710 10.1038/s41467-021-25064-x 34354070 2041-1723 8342488 2021NatCo..12.4710C free 10.1101/2021.04.30.442174 Biosynthesis 2-aminoadenine is produced in two steps. The enzyme MazZ (homologous to MazG, EC 3.6.1.8) first performs: dGTP + H2O = dGMP + diphosphate The enzyme PurZ (homologous to PurA, EC 6.3.4.4) then performs: (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 results of the altered H-bond strength in DNA and RNA October 2021 2,6-DAP was used to treat leukemia since as early as 1951.Burchenal JH Karnofsky DA Kingsley-Pillers EM Southam CM Myers WP Escher GC Craver LF Dargeon HW Rhoads CP The effects of the folic acid antagonists and 2,6-diaminopurine on neoplastic disease, with special reference to acute leukemia Cancer May 1951 4 3 549–69 10.1002/1097-0142(195105)4:3<549::aid-cncr2820040308>3.0.co;2-j 14839611 31262125 free It is known to arrest progression of cell cycle in mouse leukemia cells by 1989.Weckbecker G Cory JG Metabolic activation of 2,6-diaminopurine and 2,6-diaminopurine-2'-deoxyriboside to antitumor agents. Advances in Enzyme Regulation 1989 28 125–44 10.1016/0065-2571(89)90068-x 2624171 Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase (APRT) function,Shao C Deng L Henegariu O Liang L Stambrook PJ Tischfield JA Chromosome instability contributes to loss of heterozygosity in mice lacking p53. Proceedings of the National Academy of Sciences of the United States of America 20 June 2000 97 13 7405–10 10.1073/pnas.97.13.7405 10861008 16558 2000PNAS...97.7405S free a process shared with E. coli.Kocharian ShM Chukanova TI Sukhodolets VV [Mutations of resistance to 2,6-diaminopurine and 6-methylpurine that affect adenine phosphoribosyltransferase in Escherichia coli K-12]. Genetika 1977 13 10 1821–30 348574 DAP derivatives are in vitro antivirals useful against pseudorabies virus, a economically important livestock disease.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 Antiviral activities of 2,6-diaminopurine-based acyclic nucleoside phosphonates against herpesviruses: In vitro study results with pseudorabies virus (PrV, SuHV-1). Veterinary Microbiology 29 February 2016 184 84–93 10.1016/j.vetmic.2016.01.010 26854349 This base, in its free form, is able to correct UGA nonsense mutations by encouraging translational readthrough, through the inhibition of FTSJ1.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 2,6-Diaminopurine as a highly potent corrector of UGA nonsense mutations. Nature Communications 20 March 2020 11 1 1509 10.1038/s41467-020-15140-z free 32198346 7083880 2020NatCo..11.1509T Bioengineering In bioengineering, anti-miRNA oligonucleotides (specifically, the serinol nucleic acid [SNA] type) incorporating base Z instead of A show enhanced binding to RNA.Kamiya Y Donoshita Y Kamimoto H Murayama K Ariyoshi J Asanuma H Introduction of 2,6-Diaminopurines into Serinol Nucleic Acid Improves Anti-miRNA Performance. ChemBioChem 5 October 2017 18 19 1917–1922 10.1002/cbic.201700272 28748559 35619213 DAP is used similarly to other nuclear acid analogues in the investigation of enzyme structures and mechanisms.Bailly C The use of diaminopurine to investigate structural properties of nucleic acids and molecular recognition between ligands and DNA Nucleic Acids Research 1 October 1998 26 19 4309–4314 10.1093/nar/26.19.4309 9742229 147870 References Category:Purines Category:Nucleobases