2,6-Diaminopurine


2,6-diaminopurine is a compound once used in the treatment of leukemia. It is found instead of adenine in the genetic material of some bacteriophage viruses,
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.

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, so context is required to differentiate. AEGIS refers to this base as "AminoA" instead.
It has also been called the "D" base, but the more common interpretation of "D" is dihydrouridine.

In viruses

In cyanophage S-2L, diaminopurine is used instead of adenine. Diaminopurine base pairs perfectly with thymine as it is identical to adenine but has an amine group at position 2 forming 3 intermolecular hydrogen bonds, eliminating the major difference between the two types of basepairs. 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:
  • The S-2L phage avoids incorporating A bases in the genome by hydrolyzing dATP ;
  • The Z base is produced by a pathway involving DUF550 and PurZ in S-2L and Vibrio phage PhiVC8;
  • The PrimPol/AEP DNA polymerase responsible for handling the Z base occurs in the same gene cluster as the three aforementioned enzymes;
  • The Z base is quite widespread in both Siphoviridae and Podoviridae, based on the occurrence of the said gene cluster.
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 and PurZ are also determined, showing a possible link between PurZ and archaeal versions of PurA.

Biosynthesis

2-aminoadenine is produced in two steps. The enzyme MazZ first performs:
The enzyme PurZ then performs:
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. It is known to arrest progression of cell cycle in mouse leukemia cells by 1989. Cancer cells are known to become resistant to DAP by losing their adenine phosphoribosyltransferase function, a process shared with E. coli.
DAP derivatives are in vitro antivirals useful against pseudorabies virus, a economically important livestock disease. This base, in its free form, is able to correct UGA nonsense mutations by encouraging translational readthrough, through the inhibition of FTSJ1.

Bioengineering

In bioengineering, anti-miRNA oligonucleotides incorporating base Z instead of A show enhanced binding to RNA.
DAP is used similarly to other nuclear acid analogues in the investigation of enzyme structures and mechanisms.