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Bioorg Med Chem Lett. 2009 Dec 15;19(24):6893-7. doi: 10.1016/j.bmcl.2009.10.078. Epub 2009 Oct 23.

Multivalent binding oligomers inhibit HIV Tat-TAR interaction critical for viral replication.

Author information

1
Laboratory of Bioorganic Chemistry, NIDDK, NIH, DHHS, Bethesda, MD 20892, USA. appellad@niddk.nih.gov

Abstract

We describe the development of a new type of scaffold to target RNA structures. Multivalent binding oligomers (MBOs) are molecules in which multiple sidechains extend from a polyamine backbone such that favorable RNA binding occurs. We have used this strategy to develop MBO-based inhibitors to prevent the association of a protein-RNA complex, Tat-TAR, that is essential for HIV replication. In vitro binding assays combined with model cell-based assays demonstrate that the optimal MBOs inhibit Tat-TAR binding at low micromolar concentrations. Antiviral studies are also consistent with the in vitro and cell-based assays. MBOs provide a framework for the development of future RNA-targeting molecules.

PMID:
19896372
PMCID:
PMC2783946
DOI:
10.1016/j.bmcl.2009.10.078
[Indexed for MEDLINE]
Free PMC Article

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