4'-Acylated thymidine 5'-triphosphates: a tool to increase selectivity towards HIV-1 reverse transcriptase.

Abstract:

:4'-Acylated thymidines represent a new class of DNA chain terminators, since they have been shown to act as post-incorporation chain-terminating nucleotides despite the presence of a free 3'-hydroxyl group. Here, we describe the action of the 4'-acetyl- (MeTTP) and 4'-propanoylthymidine 5'-triphosphate (EtTTP) on HIV-1 reverse transcriptase in RNA- and DNA-dependent DNA synthesis and on DNA synthesis catalyzed by the cellular DNA polymerases alpha, beta, delta and epsilon. MeTTP exhibits a high selectivity towards HIV-1 reverse transcriptase. By the use of the bulkier propanoyl group as the 4'-substituent of the nucleoside 5'-triphosphate, selectivity towards HIV-1 reverse transcriptase could be increased without affecting substrate efficiency. Thus, 4'-modifications may serve as a tool to increase selectivity towards HIV-1 reverse transcriptase.

journal_name

Nucleic Acids Res

journal_title

Nucleic acids research

authors

Marx A,Amacker M,Stucki M,Hübscher U,Bickle TA,Giese B

doi

10.1093/nar/26.17.4063

subject

Has Abstract

pub_date

1998-09-01 00:00:00

pages

4063-7

issue

17

eissn

0305-1048

issn

1362-4962

pii

gkb611

journal_volume

26

pub_type

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