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Functional fragments of HIV-1 VPR protein and methods of using the same

Inactive Publication Date: 2006-04-27
THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Benefits of technology

[0016] The present invention further relates to methods of identifying compounds that inhibit Vpr protein binding to the p6 domain of p55 or to p6 protein. The methods comprise the steps of contacting a fragment of HIV-1 Vpr comprising amino acid sequence 17-36 or a non-HIV-1 Vpr protein comprising aminoacids 17-36 of HIV-1 Vpr protein with a protein comprising an HIV-1 Gag protein p6 domain in the presence of a test compound. The level of binding between the fragment of HIV-1 Vpr or the non-HIV-1 Vpr protein and the protein comprising an HIV-1 Gag p6 domain is determined and compared to th

Problems solved by technology

Vpr has been reported to causes growth arrest and structural defects in yeast.

Method used

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  • Functional fragments of HIV-1 VPR protein and methods of using the same
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  • Functional fragments of HIV-1 VPR protein and methods of using the same

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SUMMARY

[0101] The vpr gene product of human immunodeficiency virus type 1 (HIV-1) is a virion associated protein that is essential for efficient viral replication in monocyte / macrophages. Vpr is primarily localized in the nucleus when expressed in the absence of other viral proteins. Vpr is packaged efficiently, into viral particles through interactions with the p6 domain of the Gag precursor polyprotein p55gag. We developed a panel of expression vectors encoding Vpr molecules mutated in the amino terminal helical domain, leucine-isoleucine (LR) domain, and carboxy terminal domain to map the different functional domains and to define the interrelationships between virion incorporation, nuclear localization, cell cycle arrest, and differentiation functions of Vpr. We observed that substitution mutations in the N-terminal domain of Vpr impaired both nuclear localization and virion packaging, suggesting that the helical structure may play a vital role in modulating both of these biolo...

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Abstract

Conjugated compositions comprising a fragment of HIV-1 Vpr or a non-HIV-1 Vpr protein conjugated to a therapeutic compounds and methods of using the same to deliver therapeutic compounds to a cell's nucleus or for the preparation of drug delivery particles are disclosed. Functional fragments of HIV-1 Vpr and functional non-HIV-1 Vpr proteins, and pharmaceutical compositions comprising the same are disclosed. Methods of inhibiting cell proliferation and methods of treating an individual who has a hyperproliferative disease are disclosed. Methods of identifying compounds that inhibit Vpr protein binding to the p6 domain of p55 or to p6 protein and kits for performing such methods are disclosed.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Application Ser. No. 60 / 055,754, which is incorporated herein be reference. The present invention is related to U.S. Ser. No. 08 / 019,601 filed Feb. 19, 1993; U.S. Ser. No. 08 / 167,608 filed Dec. 15, 1993; U.S. Ser. No. 08 / 246,17 filed May 19, 1994; U.S. Ser. No. 08 / 309,644 filed Sep. 21, 1994; U.S. Ser. No. 08 / 382,873 filed Feb. 3, 1995; U.S. Ser. No. 08 / 505,196 filed Oct. 11, 1995; and U.S. Ser. No. 08 / 809,186 filed Mar. 20, 1997, which are each incorporated herein by reference.FIELD OF THE INVENTION [0002] The present invention relates to fragments of HIV-1 Vpr protein which function in nuclear localization, virion packaging, cell cycle arrest and / or cell differentiation. The present invention relates to non-Vpr proteins which comprise such fragments of HIV-1 Vpr protein. The present invention also relates to methods of using such fragments and proteins to localize proteins to a cell...

Claims

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Application Information

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IPC IPC(8): C12P21/06A61K39/12A61K47/48A61K48/00C07K14/16G01N33/569
CPCA61K47/48246A61K47/48776A61K48/00A61K2039/53C07K14/005C12N2740/16322G01N33/56988G01N2500/00A61K47/64A61K47/6901
Inventor MAHALINGAM, SUNDARASAMYAYYAVOO, VELPANDIPATEL, MAMATAKIEBER-EMMONS, THOMASWEINER, DAVID
Owner THE TRUSTEES OF THE UNIV OF PENNSYLVANIA
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