A new nucleoside analogue with potent activity against mutant sr39 Herpes Simplex Virus-1 (HSV-1) Thymidine Kinase (TK)

G. S.M. Sundaram, Scott E. Harpstrite, Jeff Lung Fa Kao, Silvia D. Collins, Vijay Sharma

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

Nucleoside analogues, such as penciclovir, ganciclovir, acyclovir, and their fluoro-substituted derivatives, have wide utility as antivirals. Among these analogues, FHBG (18F-Fluorohydroxybutylguanine) is a well-validated PET (positron emission tomography) probe for monitoring reporter gene expression. To evaluate whether or not imposing rigidity into the flexible side chain of FHBG 4 could also impact its interaction, with amino acid residues within the binding site of HSV1-TK (Herpes Simplex Virus-1 Thymidine Kinase), thus influencing its cytotoxic activity. Herein, the synthesis of a new fluorinated nucleoside analogue 6 (conceived via ligand-docking studies) is reported. Agent 6 demonstrates selective activity against HeLa cells stably transfected with mutant HSV1-sr39TK and is also 47-fold more potent than FHBG.

Original languageEnglish
Pages (from-to)3568-3571
Number of pages4
JournalOrganic Letters
Volume14
Issue number14
DOIs
StatePublished - Jul 20 2012

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