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Nucleotides, Part LIX , Synthesis, Characterization, and Biological Activities of New Potential Antiviral Agents: (2′ – 5′)Adenylate Trimer Analogs Containing 3′‐Deoxy‐3′‐(hexadecanoylamino)adenosine at the 2′‐Terminus
Author(s) -
SchirmeisterTichy Helga,
Iacono Kathryn T.,
Muto Nicholas F.,
Homan Joseph W.,
Suhadolnik Robert J.,
Pfleiderer Wolfgang
Publication year - 1999
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/(sici)1522-2675(19990407)82:4<597::aid-hlca597>3.0.co;2-v
Subject(s) - chemistry , reverse transcriptase , trimer , syncytium , stereochemistry , adenylate kinase , deoxyadenosine , adenosine , nucleotide , transcription (linguistics) , biochemistry , microbiology and biotechnology , enzyme , rna , cell , dimer , gene , linguistics , philosophy , organic chemistry , biology
Based upon 3′‐amino‐3′‐deoxyadenosine ( 15 ), its protected 3′‐hexadecanoylamino derivative 22 was chosen as starting material for the synthesis of a series of new modified 2′ – 5′‐adenylate trimers 33 – 36 as potential antiviral agents. All (2′ – 5′)A trimer analogs 33 – 36 inhibit HIV‐1 replication as measured by the inhibition of syncytia formation and inhibition of HIV‐1 reverse transcriptase activity. Compound 34 inhibits HIV‐1 reverse transcription by 100% and subsequently inhibits expression of HIV‐1 p24. However, compound 35 acts differently, since it does not inhibit HIV‐1 reverse transcription, HIV‐1 integrase, or HIV‐1 p24 expression. Therefore, 35 appears to exert its inhibitory effect at a later stage of HIV‐1 replication, i.e. , the budding process.