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Design, synthesis, and biological activity of a cyclic peptide: An inhibitor of HIV-1 Tat-TAR interactions in human cells

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BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 10, 期 9, 页码 971-974

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PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0960-894X(00)00140-2

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Replication of human immunodeficiency virus type 1 (HIV-1) requires specific interactions of Tat protein with the transactivation responsive region (TAR) RNA, a 59-base stem-loop structure located at the 5'-end of all HIV mRNAs. A number of cyclic peptides are known to possess antibiotic activity and increased biological stability. Here we report the design, synthesis, and biological activity of a cyclic peptide (2), which inhibits transcriptional activation by Tat protein in human cells with an IC50 of approximate to 40 nM. Cyclic peptides that can target specific RNA structures provide a new class of small molecules that can be used to control cellular processes involving RNA-protein interactions in vivo. (C) 2000 Elsevier Science Ltd. All rights reserved.

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