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Nucleotides Part LXX
Author(s) -
Charubala Ramamurthy,
Pfleiderer Wolfgang,
Suhadolnik Robert J.,
Iacono Kathryn T.,
Muto Nicholas F.,
Homan Joseph W.,
MartinandMari Camille,
Horvath Susan E.,
Henderson Earl E.,
Steele Amber,
Rogers Thomas J.
Publication year - 2002
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/1522-2675(200208)85:8<2284::aid-hlca2284>3.0.co;2-e
Subject(s) - chemistry , stereochemistry , nuclease , microbiology and biotechnology , enzyme , biochemistry , biology
The chemical syntheses of nuclease‐resistant, nontoxic bioactive (2′‐5′)agonists, 3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→2″)‐9‐[(2″‐hydroxyethoxy)methyl]adenine (d 3 A‐d 3 A‐d 3 A‐etherA; 36 ), 1‐benzyl‐3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→2″)‐9‐[2″‐hydroxyethoxy)methyl]adenine ( N 1 ‐benzyl‐d 3 A‐d 3 A‐d 3 A‐etherA; 37 ), N 6 ‐benzyl‐3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→5′)‐3′‐deoxyadenylyl‐(2′→2″)‐9‐[(2″‐hydroxyethoxy)methyl]adenine ( N 6 ‐benzyl‐d 3 A‐d 3 A‐d 3 A‐etherA; 38 ), N 6 ‐benzyladenylyl‐(2′→5′)‐adenylyl‐(2′→5′)‐adenylyl‐(2′→2″)‐9‐[(2″‐hydroxyethoxy)methyl]adenine ( N 6 ‐benzyl‐A‐A‐A‐etherA; 39 ), as well as the biological activities of 37, 38 , and already synthesized and published adenylyl‐(2′→5′)‐adenylyl‐(2′→5′)‐adenylyl‐(2′→2″)‐9‐[(2″‐hydroxyethoxy)methyl]adenine (A‐A‐A‐etherA; 40 ), are described. The above (2′‐5′)A derivatives 37 – 40 inhibit HIV‐1 replication as measured by inhibition of syncytia formation, HIV‐1 reverse transcriptase activity, or HIV‐1 p24‐antigen expression, with no evidence of cytotoxicity. Oligonucleotides 37, 38 , and 40 were taken up intact into T cells in culture of cytoplasmic concentrations sufficient to activate the latent endoribonuclease, RNase L. N 6 ‐Benzyl‐d 3 A‐d 3 A‐d 3 A‐etherA ( 38 ) also exerts immunostimulatory effects by increasing expression of monocyte chemotactic protein‐1 (MCP‐1), and, thereby, competing with HIV‐1 for binding to a critical HIV‐coreceptor.