(s 4dU) 35: a novel, highly potent oligonucleotide inhibitor of the human immunodeficiency virus type 1 reverse transcriptase

• Published in: FEBS letters 1996-10, Vol.396 (1), p.43-46
• Main Authors: Tökés, Szilvia, Aradi, Janos
• Format: Article
• Language: English
• Subjects: AIDS, acquired immunodeficiency syndrome; AIDS/HIV; Antitemplate; Chromatography, High Pressure Liquid; Deoxyuracil Nucleotides - chemistry; DNA Primers; HIV Reverse Transcriptase - antagonists & inhibitors; HIV, human immunodeficiency virus; Human immunodeficiency virus; Inhibition; Na-PPi, Na-pyrophosphate; Oligo 4-thio-2′-deoxyuridylate; Oligonucleotides - chemistry; Oligonucleotides - pharmacology; Reverse transcriptase; Reverse Transcriptase Inhibitors - chemistry; Reverse Transcriptase Inhibitors - pharmacology; RT, reverse transcriptase; Structure-Activity Relationship; Sulfur - chemistry; TCA, trichloroacetic acid
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/0014-5793(96)01032-0

Oligodeoxycytidylates were converted to s 4dUMP-containing oligomers by treatment with liquid H 2S. The inhibitory potency of the modified oligonucleotides on human immunodeficiency virus type 1 reverse transcriptase depended on the chain length and on the percentage of modification. The most potent reverse transcriptase inhibitor was (s 4dU) 35. The inhibitory pattern was competitive, when either poly(A)·(dT) 16 or poly(C)·(dG) 16 was used as template-primer (variable substrate), suggesting that the free enzyme interacts with (s 4dU) 35. The K i values were 3.0 and 2.2 nM in the presence of poly(A)·(dT) 16 and poly(C)·(dG) 16, respectively.