1uts
From Proteopedia
(New page: 200px<br /> <applet load="1uts" size="450" color="white" frame="true" align="right" spinBox="true" caption="1uts" /> '''DESIGNED HIV-1 TAR BINDING LIGAND'''<br /> ...) |
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'''DESIGNED HIV-1 TAR BINDING LIGAND'''<br /> | '''DESIGNED HIV-1 TAR BINDING LIGAND'''<br /> | ||
==Overview== | ==Overview== | ||
| - | The targeting of RNA for the design of novel anti-viral compounds | + | The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation. |
==About this Structure== | ==About this Structure== | ||
| - | 1UTS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with P13 as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http:// | + | 1UTS is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/ ] with <scene name='pdbligand=P13:'>P13</scene> as [http://en.wikipedia.org/wiki/ligand ligand]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=1UTS OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Davis, B.]] | [[Category: Davis, B.]] | ||
[[Category: Karn, J.]] | [[Category: Karn, J.]] | ||
| - | [[Category: Murchie, A | + | [[Category: Murchie, A I.H.]] |
[[Category: P13]] | [[Category: P13]] | ||
[[Category: antiviral]] | [[Category: antiviral]] | ||
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[[Category: tar rna]] | [[Category: tar rna]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 15:28:14 2008'' |
Revision as of 13:28, 21 February 2008
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DESIGNED HIV-1 TAR BINDING LIGAND
Overview
The targeting of RNA for the design of novel anti-viral compounds represents an area of vast potential. We have used NMR and computational methods to model the interaction of a series of synthetic inhibitors of the in vitro RNA binding activities of a peptide derived from the transcriptional activator protein, Tat, from human immunodeficiency virus type 1. Inhibition has been measured through the monitering of fluorescence resonance energy transfer between fluorescently labeled peptide and RNA components. A series of compounds containing a bi-aryl heterocycle as one of the three substituents on a benzylic scaffold, induce a novel, inactive TAR conformation by stacking between base-pairs at the site of a three-base bulge within TAR. The development of this series resulted in an enhancement in potency (with Ki < 100 nM in an in vitro assay) and the removal of problematic guanidinium moieties. Ligands from this series can act as inhibitors of Tat-induced transcription in a cell-free system. This study validates the drug design strategy of using a ligand to target the RNA receptor in a non-functional conformation.
About this Structure
1UTS is a Single protein structure of sequence from [1] with as ligand. Full crystallographic information is available from OCA.
Reference
Structure-based drug design targeting an inactive RNA conformation: exploiting the flexibility of HIV-1 TAR RNA., Murchie AI, Davis B, Isel C, Afshar M, Drysdale MJ, Bower J, Potter AJ, Starkey ID, Swarbrick TM, Mirza S, Prescott CD, Vaglio P, Aboul-ela F, Karn J, J Mol Biol. 2004 Feb 20;336(3):625-38. PMID:15095977
Page seeded by OCA on Thu Feb 21 15:28:14 2008
Categories: Single protein | Aboul-Ela, F. | Davis, B. | Karn, J. | Murchie, A I.H. | P13 | Antiviral | Conformational change | Drug design | Hiv-1 | Ligand binding | Tar rna
