The synthesis and adenosine deaminase activity of two analogues of ganciclovir

Author

Kathy Alewine Lee

Date of Award

5-1993

Degree Type

Thesis

Degree Name

Master of Science

Major

Chemistry

Major Professor

David C. Baker

Committee Members

Ronald M. Magid, George W. Kabalka

Abstract

In an attempt to produce a prodrug which is effectively transported across the blood-brain barrier, two analogues of ganciclovir were synthesized and their adenosine deaminase (ADA) activity was determined. 2-Amino-6-chloro-9-[(1,3- dihydroxy-2-propoxy)methyl] purine (6-Cl-DHPG) and 2-amino-6-methoxy-9- [(1,3-dihydroxy-2-propoxy)methyl] purine (6-MeO-DHPG) were synthesized from guanine. An alternate route for the synthesis of an intermediate was investigated in an attempt to improve the yield; however, ambiguous results were obtained. Both substrates were shown to be enzymatically converted to ganciclovir. The Michaelis-Menten parameters for the hydrolysis of 6-CI-DHPG (Κ_Μ = 313 µΜ, V_max = 1.27 × 10^-6) and 6-MeO-DHPG (K_M = 345 µM, V_max = 5.05 × 10^-5) were determined by continuous spectrophotometric (CS) assay.

Recommended Citation

Lee, Kathy Alewine, "The synthesis and adenosine deaminase activity of two analogues of ganciclovir. " Master's Thesis, University of Tennessee, 1993.
https://trace.tennessee.edu/utk_gradthes/11939