2,6-Diaminopurine

2,6-diaminopurine (2,6-DAP, also known as 2-aminoadenine, standard IUPAC symbol n²A^{[1]: N4.1, N4.4}) is a compound once used in the treatment of leukemia.^[2] It is found instead of adenine (A) in the genetic material of some bacteriophage viruses,^[3]

2,6-Diaminopurine

Names
IUPAC name 7H-purine-2,6-diamine
Other names 2-aminoadenine; 2,6-DAP
Identifiers
CAS Number	1904-98-9 Y
3D model (JSmol)	Interactive image
ChEMBL	ChEMBL388596 Y=
ChemSpider	28738 Y
ECHA InfoCard	100.016.006
PubChem CID	30976
UNII	49P95BAU4Z Y
CompTox Dashboard (EPA)	DTXSID0062052
InChI 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 Nc1nc(N)nc2c1nc[nH]2
Properties
Chemical formula	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)
Solubility in water	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 ?) 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.^[4][5][6]

Abbreviations

In virology it is referred to as the "Z" base.^[7] 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.^[8] AEGIS refers to this base as "AminoA" instead.^[9]

It has also been called the "D" base,^[10][11] but the more common interpretation of "D" is dihydrouridine.^[12]

In viruses

Main article: nucleic acid analogues

DiampurineT DNA base pair

In cyanophage S-2L (Siphoviridae), diaminopurine is used instead of adenine (host evasion).^[13] 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:^[14]

• The S-2L phage avoids incorporating A bases in the genome by hydrolyzing dATP (DatZ enzyme);^[15]
• The Z base is produced by a pathway involving DUF550 (MazZ) and PurZ in S-2L and Vibrio phage PhiVC8;^[7]
• The PrimPol/AEP DNA polymerase responsible for handling the Z base occurs in the same gene cluster as the three aforementioned enzymes;^[16]
• The Z base is quite widespread in both Siphoviridae and Podoviridae, based on the occurrence of the said gene cluster.^[17]

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.^[18]

Biosynthesis

2-aminoadenine is produced in two steps. The enzyme MazZ (homologous to MazG, EC 3.6.1.8) first performs:^[18]

dGTP + H₂O = dGMP + diphosphate

The enzyme PurZ (homologous to PurA, EC 6.3.4.4) then performs:^[7]

(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

2,6-DAP was used to treat leukemia since as early as 1951.^[19] It is known to arrest progression of cell cycle in mouse leukemia cells by 1989.^[20] Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase (APRT) function,^[21] a process shared with E. coli.^[22]

DAP derivatives are in vitro antivirals useful against pseudorabies virus, a economically important livestock disease.^[23] This base, in its free form, is able to correct UGA nonsense mutations by encouraging translational readthrough, through the inhibition of FTSJ1.^[24]

Bioengineering

In bioengineering, anti-miRNA oligonucleotides (specifically, the serinol nucleic acid [SNA] type) incorporating base Z instead of A show enhanced binding to RNA.^[25]

DAP is used similarly to other nuclear acid analogues in the investigation of enzyme structures and mechanisms.^[26]