Nucleotides Synthesis and Biological Activity of (2'-5')Oligoadenylate Trimers Containing a 5'-Terminal 5'-Amino-5'-deoxy- or 5'-Amino-3',5'-dideoxyadenosine Dervative

摘要

The new (2'-5')oligoadenylate trimers 26-34 containing 5'-amino-5'-deoxyadenosine or 5'-amino-3',5'-dideoxyadenosine or their lipophlic 5'-deoxy-5'-(hexadecanoylamino) derivatives at the 5'-terminus,and adenosine or 3'-deoxyadenosine(=cordycepin) at the penultimate and 2'-end position of the trimers were synthesized by the phosphoramidite method.The newly synthesized trimers 26-34 inhibited,at 100 #mu#M concentration,.HIV-1-induced syncytia formation (SYN)by 19-96% and reverse-transcriptase activity (RT) by 27-100% (see Table).The two hexadecanoylamino derivatives 27 and 30 which were found to be potent inhibitors of SYN and RT showed also a 73 and 49% inhibition,respectively,of expression of HIV-1 p24 antigen (p24-EX).The same compounds 27 and 30 inhibited also,with a 100% efficacy,an amplification of HIV-1 partial reverse transcripts(PCR) and HIV-1 integrase activity(INT),respectively.