Resolution of racemic carbocyclic analogues of purine nucleosides through the action of adenosine deaminase. Antiviral activity of the carbocyclic 2'-deoxyguanosine enantiomers.

Academic Article

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.
  • Published In

    Keywords

  • 2-Aminopurine, Adenosine, Adenosine Deaminase, Animals, Antiviral Agents, Cytopathogenic Effect, Viral, Deoxyguanosine, Nucleoside Deaminases, Purine Nucleosides, Simplexvirus, Stereoisomerism, Structure-Activity Relationship, Vero Cells
  • Pubmed Id

  • 10708557
  • Author List

  • Secrist JA; Montgomery JA; Shealy YF; O'Dell CA; Clayton SJ
  • Start Page

  • 746
  • End Page

  • 749
  • Volume

  • 30
  • Issue

  • 4