Metabolism of the carbocyclic analogue of (E)-5-(2-iodovinyl)-2'-deoxyuridine in herpes simplex virus-infected cells. Incorporation of C-IVDU into DNA.
The carbocyclic analogues of (E)-5-(2-bromovinyl)-2'-deoxyuridine (BVDU) and (E)-5-(2-iodovinyl)-2'-deoxyuridine (IVDU), in which the sugar moiety is replaced by a cyclopentane ring and which have been designated as C-BVDU and C-IVDU, respectively, are, like their parent compounds BVDU and IVDU, potent and selective inhibitors of herpes simplex virus type 1 (HSV-1) and, to a lesser extent, herpes simplex virus type 2 (HSV-2) replication. We have now synthesized the radiolabeled C-IVDU analogue, C-[125I]IVDU, and determined its metabolism by HSV-infected and mock-infected Vero cells. C-[125I]IVDU was effectively phosphorylated by HSV-1-infected cells and, to a lesser extent, HSV-2-infected cells. C-[125I]IVDU was not phosphorylated to an appreciable extent by either mock-infected cells or cells that had been infected with a thymidine kinase-deficient mutant of HSV-1. Furthermore, C-[125I]IVDU was incorporated into both viral and cellular DNA of HSV-1-infected Vero cells. This finding represents the first demonstration of the incorporation of a cyclopentylpyrimidine into DNA.
De Clercq
E
E
Bernaerts
R
R
Balzarini
J
J
Herdewijn
P
P
Verbruggen
A
A
D000818:Animals; D002460:Cell Line; D002472:Cell Transformation, Viral; D002522:Chlorocebus aethiops; D002855:Chromatography, Thin Layer; D003517:Cyclopentanes / Q000138:chemical synthesis / Q000378:metabolism*; D004247:DNA / Q000096:biosynthesis* / Q000302:isolation & purification; D004279:DNA, Viral / Q000096:biosynthesis; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D007457:Iodine Radioisotopes; D007668:Kidney; D018139:Simplexvirus / Q000378:metabolism*
D003517:Cyclopentanes; D004279:DNA, Viral; D007457:Iodine Radioisotopes; D004247:DNA; C045201:1-(3-hydroxy-4-(hydroxymethyl)cyclopentyl)-5-(2-iodovinyl)-2,4-(1H,3H)-pyrimidinedione; D003857:Deoxyuridine