Adenine analogues

It has been further suggested that exogenous adenine is converted to AMP and assimilated into nucleic acid at a discrete locus separate from the pathway immediately accessible to endogenous purines [106], a point which could have important bearing on the biologic activity of adenine analogues. 

The cytostatic drugs administered (indicated by a syringe in the illustration) are often not active themselves but are only converted into the actual active agent in the metabolism. This also applies to the adenine analogue 6-mercaptopurine, which is initially converted to the mononucleotide tIMP (thioinosine monophosphate). Via several intermediate steps, tIMP gives rise to tdGTP, which is incorporated into the DNA and leads to crosslinks and other anomalies in it. The second effective metabolite of 6-mercaptopurine is S-methylated tIMP, an inhibitor of amidophos-phoribosyl transferase (see p. 188). 

Adefovir is an adenine analogue reverse transcriptase inhibitor. While it has activity against both HIV and hepatitis B, its use in HIV infection is limited by nephrotoxicity due to the high doses needed (1). The dose used for treatment of hepatitis B is about one-tenth that needed to treat HIV infection, so patients with hepatitis B must have co-infection with HIV ruled out before treatment is started. 

Tri- and tetracyclic adenine analogues as dimensional probes of enzyme coenzyme binding sites 82ACR128. 

The enantiomeiically-pure cyclopropane 245 has been described,336 as has the adenine analogue of opposite chirality, together with other similar racemic species,337 and the analogue 246, prepared by treatment of 1-cyanomethyluracil with LDA, followed by q>ibromohydiin.338... 

Figure 1 Reactions used to study electron transfer in DNA with photophysical methods. (A) Photoinduced reduction of Rh(phi)2bpy by Et [12]. (B) Triplet energy transfer (TET, a double electron transfer) from Ru(phen)(bpy)(Me2-dppz) " to Os(phen)(bpy) (Me2-dppz) + [13]. (C) Photoinduced oxidation of Z by Et [14-15]. (D) Photoinduced oxidation of G by adenine analogues ( A [16])-...

Both analogues can sm e to iUustrate an important problem frequently associated with design of new biologically active nucleoside analogues, namely, base selectivity. Thus, the antiviral effect of acyclovir (la), a guanine derivative, is unique. The corresponding adenine analogue (Ic), which is historically the first compound of this series, is much less effective. The thymine and cytosine derivatives lb. Id have virtually no antiviral activity. ... 

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