Structural effects on the phosphorylation of 3-substituted 1-beta-D-ribofuranosyl-1,2,4-triazoles by human adenosine kinase.
The conversion of ribavirin to the monophosphate by adenosine kinase is the rate-limiting step in activation of this broad spectrum antiviral drug. Variation of the 3-substituents in a series of bioisosteric and homologated 1-beta-D-ribofuranosyl-1,2,4-triazoles has marked effects on activity with the human adenosine kinase, and analysis of computational descriptors and binding models offers insight for the design of novel substrates.
Kumarapperuma
Sidath C
SC
Department of Chemistry and Biochemistry, MSC 3C, New Mexico State University, Las Cruces, NM 88003, USA.
Sun
Yanjie
Y
Jeselnik
Marjan
M
Chung
Kiwon
K
Parker
William B
WB
Jonsson
Colleen B
CB
Arterburn
Jeffrey B
JB
D000248:Adenosine Kinase / Q000378:metabolism*; D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*; D003201:Computers; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D010766:Phosphorylation; D012254:Ribavirin / Q000031:analogs & derivatives*; D013237:Stereoisomerism; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism*
D000998:Antiviral Agents; D014230:Triazoles; D012254:Ribavirin; D000248:Adenosine Kinase