Nucleosides. Part LX. Synthesis and Characterization of Monomeric Cordycepin-Vitamin and Cordycepin-Lipid Conjugates Model Substances for Biodegradable Ester and Carbonate Linkages in Conjugates and Potential Inhibitors of HIV-1 Replication
✍ Scribed by Marita Wasner; Wolfgang Pfleiderer; Robert J. Suhadolnik; Susan E. Horvath; Ning Kon; Ming-Xu Guan; Earl E. Henderson; Robert J. Suhadolnik; Earl E. Henderson; Martin E. Adelson
- Book ID
- 102859915
- Publisher
- John Wiley and Sons
- Year
- 1996
- Tongue
- German
- Weight
- 783 KB
- Volume
- 79
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Hans-Jiirgen Bestmann on the occasion of his 70th birthday and in admiration to his interesting contribution to organic chemistry (2.1.96) Monomeric 3'-deoxyadenosine (cordycepin) was modified at the 2-0 -(13-18) and S'-O-position (25-29) by the vitamins E, D,, and A and by the two lipids 1,2-di-O-palmitoylglycerol and 1,2-di-O-hexadecylglycerol via succinate or carbonate linkages. These base-labile conjugates afforded protection groups like the 2-(4-nitro-pheny1)ethoxycarbonyl (npeoc) and monomethoxytrityl group (MeOTr) that are cleavable without harming the ester and carbonate bonds, respectively. Monomeric conjugates of cordycepin and vitamin E, vitamin D,, 1,2-di-0-palmitoylglycerol, and 1,2-di-O-hexadecylglycerol (see 13, 14, 17, 18, 25, 26, 28, and 29) inhibited HIV-l-induced syncytia formation 1.7 to 6.2 fold compared to 1.5-fold for cordycepin (see Table ); ICsO values for 25 and 28 were 257 and 267 p ~, respectively. In addition, the monomeric cordycepin-vitamin and -lipid conjugates inhibited HIV-1 RT activity 2 8 4 9 % which compares with a 13% inhibition of HIV-1 RT observed for cordycepin. The minimal inhibition of HIV-I-induced syncytia formation and HIV-1 RT activity did not proceed by the activation of RNase L. The monomeric conjugates tested (13, 14) increased PKR expression.