title: Resolution of racemic carbocyclic analogues of purine nucleosides through the action of adenosine deaminase. Antiviral activity of the carbocyclic 2'-deoxyguanosine enantiomers.
abstract: The action of adenosine deaminase on racemic carbocyclic analogues of 6-aminopurine nucleosides was investigated. When either racemic carbocyclic adenosine [(+/-)-C-Ado] or the racemic carbocyclic analogue [(+/-)-C-2,6-DAP-2'-dR] of 2,6-diaminopurine 2'-deoxyribofuranoside was incubated with this enzyme, approximately half of the material was deaminated rapidly. From the resulting solution, the D isomers of the deaminated carbocyclic analogues (D-carbocyclic inosine, D-C-Ino, or D-carbocyclic 2'-deoxyguanosine, D-2'-CDG) and the L isomers of the undeaminated carbocyclic analogues were isolated. At higher concentrations of the enzyme, deamination of L-C-Ado and L-C-2,6-DAP-2'-dR proceeded slowly, thus also making the other enantiomers accessible. In tests in vitro against herpes simplex virus, types 1 and 2, D-2'-CDG was as active and potent as (+/-)-2'-CDG, whereas L-2'-CDG displayed only modest activity. In contrast to the previously reported high activity and potency of (+/-)-C-2,6-DAP-2'-dR against these two viruses, L-C-2,6-DAP-2'-dR was inactive.
mesh_terms: D015075:2-Aminopurine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000302:isolation & purification / Q000378:metabolism; D000243:Adenosine Deaminase / Q000378:metabolism*; D000818:Animals; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000494:pharmacology*; D009700:Nucleoside Deaminases / Q000378:metabolism*; D011684:Purine Nucleosides / Q000302:isolation & purification* / Q000378:metabolism; D018139:Simplexvirus / Q000187:drug effects*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014709:Vero Cells
chemical_list: D000998:Antiviral Agents; D011684:Purine Nucleosides; C030034:aristeromycin; D015075:2-Aminopurine; D009700:Nucleoside Deaminases; D000243:Adenosine Deaminase; D003849:Deoxyguanosine; D000241:Adenosine