In:
Canadian Journal of Chemistry, Canadian Science Publishing, Vol. 82, No. 4 ( 2004-04-01), p. 513-523
Abstract:
Suicide gene therapy with the herpes simplex virus type-1 thymidine kinase gene (HSV-1 tk) is considered to be a promising approach to the treatment of cancer. Making use of the lower specificity of the viral enzyme compared to human thymidine kinase, the therapy involves the administration of antiviral agents (e.g., ganciclovir) as prodrugs to induce enzymatic cell death in those cells that express the transferred gene. 18 F-labelled derivatives have been described for monitoring location, duration, and magnitude of the viral kinase enzyme activity by positron emission tomography (PET). Since an optimal radiotracer has not been developed, novel substances were synthesized for monitoring gene expression. A group of 13 nucleoside analogues were synthesized, among them N 1 -methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]guanine (5) and N 1 -methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]guanine (7) as methyl analogues of ganciclovir and penciclovir and their related fluoro compounds (6, 8). Further novel derivatives include N 6 -methyl-9-[(1,3-dihydroxy-2-propoxy)methyl]-, N 6 -methyl-9-[(4-hydroxy)-3-hydroxymethylbutyl]adenine (9, 10), as well as the uracil derivatives 5-hydroxy-1-[(1,3-dihydroxy-2-propoxy)methyl] uracil (11), 6-methyl-1-[(1,3-dihydroxy-2-propoxy)-methyl]uracil (12), and its 3-fluoro-derivative (13).Key words: fluorinated nucleoside analogues, gene therapy, PET, thymidine kinase.
Type of Medium:
Online Resource
ISSN:
0008-4042
,
1480-3291
Language:
English
Publisher:
Canadian Science Publishing
Publication Date:
2004
detail.hit.zdb_id:
1482256-8
