Identification of Peptide Ligands for Target RNA Structures Derived from the HIV-1 Packaging Signal ψ by Screening Phage-Displayed Peptide Libraries

ChemBioChem ◽  
2003 ◽  
Vol 4 (10) ◽  
pp. 1093-1097 ◽  
Author(s):  
Anette Pustowka ◽  
Julia Dietz ◽  
Jan Ferner ◽  
Michael Baumann ◽  
Margot Landersz ◽  
...  
Keyword(s):  
Peptide Ligands ◽  
Peptide Libraries ◽  
Rna Structures ◽  
Packaging Signal ◽  
Target Rna ◽  
Hiv 1

Structure and Stability of Wild-type and Mutant RNA Internal Loops from the SL-1 Domain of the HIV-1 Packaging Signal

2002 ◽  
Vol 322 (3) ◽  
pp. 543-557 ◽  
Author(s):  
Jane Greatorex ◽  
José Gallego ◽  
Gabriele Varani ◽  
Andrew Lever
Keyword(s):  
Wild Type ◽  
Packaging Signal ◽  
Structure And Stability ◽  
Internal Loops ◽  
Hiv 1

Quantitative Structure Activity Relationship (QSAR) study predicts small molecule binding to RNA structure

2021 ◽  
Author(s):  
Zhengguo Cai ◽  
Martina Zafferani ◽  
Olanrewaju Akande ◽  
Amanda Hargrove
Keyword(s):  
High Resolution ◽  
Small Molecules ◽  
Small Molecule ◽  
Rna Structure ◽  
Quantitative Structure ◽  
Rna Structures ◽  
Qsar Study ◽  
Structure Activity ◽  
Qsar Models ◽  
Hiv 1

The diversity of RNA structural elements and their documented role in human diseases make RNA an attractive therapeutic target. However, progress in drug discovery and development has been hindered by challenges in the determination of high-resolution RNA structures and a limited understanding of the parameters that drive RNA recognition by small molecules, including a lack of validated quantitative structure-activity relationships (QSAR). Herein, we developed QSAR models that quantitatively predict both thermodynamic and kinetic-based binding parameters of small molecules and the HIV-1 TAR model RNA system. A set of small molecules bearing diverse scaffolds was screened against the HIV-1-TAR construct using surface plasmon resonance, which provided the binding kinetics and affinities. The data was then analyzed using multiple linear regression (MLR) combined with feature selection to afford robust models for binding of diverse RNA-targeted scaffolds. The predictivity of the model was validated on untested small molecules. The QSAR models presented herein represent the first application of validated and predictive 2D-QSAR using multiple scaffolds against an RNA target. We expect the workflow to be generally applicable to other RNA structures, ultimately providing essential insight into the small molecule descriptors that drive selective binding interactions and, consequently, providing a platform that can exponentially increase the efficiency of ligand design and optimization without the need for high-resolution RNA structures.

Structure of SL4 RNA from the HIV-1 Packaging Signal†,‡

Biochemistry ◽  
2001 ◽  
Vol 40 (48) ◽  
pp. 14518-14529 ◽  
Author(s):  
Deborah J. Kerwood ◽  
Michael J. Cavaluzzi ◽  
Philip N. Borer
Keyword(s):  
Packaging Signal ◽  
Hiv 1

scholarly journals In vitro-selected RNA cleaving DNA enzymes from a combinatorial library are potent inhibitors of HIV-1 gene expression

2000 ◽  
Vol 352 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Bandi SRIRAM ◽  
Akhil C. BANERJEA
Keyword(s):  
Gene Expression ◽  
Mammalian Cell ◽  
Specific Gene ◽  
Cleavage Sites ◽  
Dna Enzymes ◽  
Biological Tool ◽  
Catalytic Motif ◽  
Target Rna ◽  
Hiv 1

Selective inactivation of a target gene by antisense mechanisms is an important biological tool to delineate specific functions of the gene product. Approaches mediated by ribozymes and RNA-cleaving DNA enzymes (DNA enzymes) are more attractive because of their ability to catalytically cleave the target RNA. DNA enzymes have recently gained a lot of importance because they are short DNA molecules with simple structures that are expected to be stable to the nucleases present inside a mammalian cell. We have designed a strategy to identify accessible cleavage sites in HIV-1 gag RNA from a pool of random DNA enzymes, and for isolation of DNA enzymes. A pool of random sequences (all 29 nucleotides long) that contained the earlier-identified 10Ő23 catalytic motif were tested for their ability to cleave the target RNA. When the pool of random DNA enzymes was targeted to cleave between any A and U nucleotides, DNA enzyme 1836 was identified. Although several DNA enzymes were identified using a pool of DNA enzymes that was completely randomized with respect to its substrate-binding properties, DNA enzyme-1810 was selected for further characterization. Both DNA enzymes showed target-specific cleavage activities in the presence of Mg2+ only. When introduced into a mammalian cell, they showed interference with HIV-1-specific gene expression. This strategy could be applied for the selection of desired target sites in any target RNA.

ANTIVIRAL ACTIVITY OF STERIC-BLOCK OLIGONUCLEOTIDES TARGETING THE HIV-1 TRANS-ACTIVATION RESPONSE AND PACKAGING SIGNAL STEM-LOOP RNAS

2005 ◽  
Vol 24 (5-7) ◽  
pp. 393-396 ◽  
Author(s):  
Douglas Brown ◽  
Andrey A. Arzumanov ◽  
John J. Turner ◽  
Dmitry A. Stetsenko ◽  
Andrew M. L. Lever ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Packaging Signal ◽  
Stem Loop ◽  
Activation Response ◽  
Hiv 1

Binding properties of SH3 peptide ligands identified from phage-displayed random peptide libraries

1996 ◽  
Vol 2 (1-2) ◽  
pp. 5-12 ◽  
Author(s):  
Noah G. Hoffman ◽  
Andrew B. Sparks ◽  
J. Mark Carter ◽  
Brian K. Kay
Keyword(s):  
Peptide Ligands ◽  
Peptide Libraries ◽  
Binding Properties ◽  
Random Peptide ◽  
Random Peptide Libraries

The major HIV-1 packaging signal is an extended bulged stem loop whose structure is altered on interaction with the gag polyprotein

2000 ◽  
Vol 301 (5) ◽  
pp. 1315
Author(s):  
Amanda Zeffman ◽  
Stuart Hassard ◽  
Gabriele Varani ◽  
Andrew Lever
Keyword(s):  
Packaging Signal ◽  
Stem Loop ◽  
Gag Polyprotein ◽  
Hiv 1

scholarly journals Nucleolin and the Packaging Signal, ψ, Promote the Budding of Human Immunodeficiency Virus Type-1 (HIV-1)

2004 ◽  
Vol 48 (2) ◽  
pp. 111-118 ◽  
Author(s):  
Tomonori Ueno ◽  
Kenzo Tokunaga ◽  
Hirofumi Sawa ◽  
Masae Maeda ◽  
Joe Chiba ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Packaging Signal ◽  
Immunodeficiency Virus ◽  
Hiv 1
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