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Synthesis of Multivalent Ligands Designed to Disrupt HIV‐1 Tat‐peptide/TAR‐RNA Interactions
Author(s) -
Scott Shakara L,
Allgaier Josh,
KosinskiCollins Melissa
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.809.1
Subject(s) - rna , tar (computing) , chemistry , transcription (linguistics) , hiv long terminal repeat , förster resonance energy transfer , agmatine , polymerase , microbiology and biotechnology , dna , biophysics , biochemistry , arginine , biology , fluorescence , amino acid , gene , gene expression , long terminal repeat , linguistics , philosophy , physics , quantum mechanics , computer science , programming language
Multiple targets exist in the development of HIV‐1 anti‐viral drugs, one of which includes the interaction between the transcriptional activator protein (Tat) and the Trans Activation Response (TAR) element of RNA. During transcription, TAR RNA, a 59‐base stem‐loop structure, located at the 5'end of all HIV‐1 mRNAs recruits Tat. Prior research has shown that the arginine rich motif (ARM) of Tat is integral to the binding interaction between the Tat‐peptide and TAR‐RNA. In the absence of Tat, the transcription machinery is rendered inept and the polymerase releases the DNA prematurely. We sought to design synthetic polymers that would disrupt the necessary interaction between Tat and TAR‐RNA, hindering HIV replication. To target the TAR‐RNA, we sought to replicate the basic ARM of Tat by functionalizing the polymer scaffolds derived from the Ring‐Opening Metathesis Polymerization (ROMP) with arginine and agmatine molecules. A Fluorescence Resonance Energy Transfer (FRET) assay is being developed to evaluate the inhibitory effects of these multivalent guanidinium displays. Continued work includes optimization of the assay and synthesis of other multivalent ligands designed to target TAR‐RNA.