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]
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/AEPDNA 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
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]
The resulting dSMP is processed by host enzymes analogously to
adenylosuccinate to produce dZTP.
In cellular life
This 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]
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]
^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.