AIDSWEEKLY Plus; Monday, November 10, 2003
Staff Medical Writers

In a recent study from the United States, "Eight adenosine analogs, 3-deaza-adenosine (DZA), 3-deaza-(±)aristeromycin (DZAri), 2',3'-dideoxy-adenosine (ddAdo), 2',3'-dideoxy-3-deaza-adenosine (ddDZA), 2',3'-dideoxy-3-deaza-(±)aristeromycin (ddDZAri), 3-deaza-5'-(±)noraristeromycin (DZNAri), 3-deaza-neplanocin A (DZNep), and neplanocin A (NepA), were tested as inhibitors of human placenta S-adenosylhomocysteine (AdoHcy) hydrolase."

"The order of potency for the inhibition of human placental AdoHcy hydrolase was: DZNep approximate to NePA >> DZAri approximate to DZNAri > DZA >> ddAdo approximate to ddDZA approximate to ddDZAri," according to R.K. Gordon and coauthors at the University of Texas.

"These same analogs were examined for their anti-HIV-1 activities measured by the reduction in p24 antigen produced by 3'-azido-3'-deoxythymidine (AZT)-sensitive HIV-1 isolates, A012 and A018, in phytohemagglutinin-stimulated peripheral blood mononuclear (PBMCs) cells," they wrote in the European Journal of Biochemistry. "Interestingly, DZNAri and the 2',3'-dideoxy 3-deaza-nucleosides (ddAdo, ddDZAri, and ddDZA) were only marginal inhibitors of p24 antigen production in HIV-1 infected PBMC."

"DZNAri is unique because it is the only DZA analog with a deleted methylene group that precludes anabolic phosphorylation," the report indicated. "In contrast, the other analogs were potent inhibitors of p24 antigen production by both HIV-1 isolates. Thus it was postulated that these nucleoside analogs could exert their antiviral effect via a combination of anabolically generated nucleotides (with the exception of DZNAri), which could inhibit reverse transcriptase or other viral enzymes, and the inhibition of viral or cellular methylation reactions."

"Additionally, QSAR-like models based on the molecular mechanics (MM) were developed to predict the order of potency of eight adenosine analogs for the inhibition of human AdoHcy hydrolase," the researchers concluded. "In view of the potent antiviral activities of the DZA analogs, this approach provides a promising tool for designing and screening of more potent AdoHcy hydrolase inhibitors and antiviral agents."

Gordon and colleagues published their study in the European Journal of Biochemistry (Anti-HIV-1 activity of 3-deaza-adenosine analogs - Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners. Eur J Biochem. 2003 Sep;270(17):3507-17.

For additional information, contact K. Ginalski, University of Texas, Southwest Medical Center, Department of Biochemistry, 5323 Harry Hines Blvd., Dallas, TX 75390, USA.

The publisher of the European Journal of Biochemistry can be contacted at: Blackwell Publishing Ltd., 9600 Garsington Rd., Oxford OX4 2DG, UK.

The information in this article comes under the major subject areas of AIDS & HIV and Pharmaceutical & Drug Development.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Gordon RK, Ginalski K, Rudnicki WR, et al., "Anti-HIV-1 activity of 3-deaza-adenosine analogs. Inhibition of S-adenosylhomocysteine hydrolase and nucleotide congeners", Eur J Biochem. 2003 Sep;270(17):3507-17

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