Nucleotides - Part LVIII - Synthesis and biological activity of (2 '-5 ')oligoadenylate trimers containing a 5 '-terminal 5 '-amino-5 '-deoxy- or 5 '-amino-3 ',5 '-dideoxyadenosine derivative

The new (2'-5')oligoadenylate trimers 26-34 containing 5'-amino-5'-deoxyade nosine or 5'-amino-3',5'- dideoxyadenosine or their lipophilic 5'-deoxy-5'- (hexadecanoylamino) derivatives at the 5'-terminus and adenosine or 3'-deox yadenosine (= cordycepin) at the penultimate and 2'-end position of the tri mers 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 f ound to be potent inhibitors of SYN and RT showed also a 73 and 49% inhibit ion, respectively, of expression of HIV-1 p24 antigen (p24-EX). The same co mpounds 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.