Compounds which inhibit HIV replication

Details Compounds which inhibit HIV replication Compounds which inhibit HIV replication

1995-06-02

2003-06-03

Celsa, Bennett (Department: 1639)

Chemistry: molecular biology and microbiology

Virus or bacteriophage, except for viral vector or...

C424S188100, C424S208100, C530S324000, C530S806000, C514S012200

Reexamination Certificate

active

06573078

ABSTRACT:

INTRODUCTION
This invention relates to human immunodeficiency virus (HIV) protein fragments which have antiviral activity, and particularly relates to HIV peptides derived from the HIV transmembrane glycoprotein (gp41) which inhibit HIV-induced cell-cell fusion. This invention further relates to methods for the inhibition of enveloped viral infection, and to methods that modulate biochemical processes which involve coiled coil peptide interactions.
BACKGROUND OF THE INVENTION
Numerous HIV protein fragments, or peptides, have been identified in an effort to develop an effective HIV vaccine. See generally B. Spalding,
Biotechnology
10, 24 (Jan. 1992). Examples of patent applications which are directed to antigenic epitopes of the gp41protein include J. Rosen et al., PCT Application WO 87/06005 and R. Duncan, EPO Application 0 371 817. To date, the development of an anti-HIV vaccine has been difficult.
N. Qureshi et al., Aids 1990 4, 553-558, describe a segment of the HIV transmembrane protein (designated “gp41”) which inhibits T-cell activation in vitro. This segment, designated “CS3”, when conjugated to human serum albumin and labeled with fluorescein, binds specifically to CD4+ cell lines, and is said to have antiviral activity. CS3 comprises amino acids 581 to 597 of the gp41protein.
B. Kemp et al., EPO Application 0 323 157, describes a fragment comprised of amino acids 572 to 591 of the gp41protein which is said to have antiviral activity.
SUMMARY OF THE INVENTION
A first aspect of the present invention is a peptide selected from the group consisting of: (a) the peptide DP-107, which has the formula, from amino terminus to carboxy terminus, of:
NNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQ (SEQ ID NO: 1); and (b) peptides of from 14 to 60 amino acids in length which form a heterodimer with the peptide DP-107 (SEQ ID NO: 1) (hereinafter on occasion referred to as “active compounds”).
A second aspect of the present invention is a process for inhibiting HIV-induced cell fusion. The process comprises contacting to an HIV-infected cell an effective fusion-inhibiting amount of a peptide selected from the group consisting of: (a) the peptide DP-107, which has the formula, from amino terminus to carboxy terminus, of:
NNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQ (SEQ ID NO: 1); and (b) peptides of from about 14 to 60 amino acids in length which form a heterodimer with the peptide DP-107 (SEQ ID NO: 1).
A third aspect of the present invention is a process for testing compounds for the ability to inhibit the ability of HIV to infect cells. The process comprises (a) contacting a test compound to a multimer of a peptide selected from the group consisting of: (i) the peptide DP-107, which has the formula, from amino terminus to carboxy terminus of:
NNLLRAIEAQQHLLQLTVWGIKQLQARILAVERYLKDQ (SEQ ID NO: 1) ; and (ii) peptides of from 14 to 60 amino acids in length which form a heterodimer with the peptide DP-107 (SEQ ID NO: 1); and then (b) detecting whether the test compound disrupts said multimer, the ability of the test compound to disrupt the multimer indicating the test compound is capable of inhibiting HIV infection of cells.
A further aspect of the invention is a method for inhibiting enveloped viral infection comprising contacting an uninfected cell with an effective amount of a peptide capable of contributing to the formation of a coiled coil peptide structure so that an enveloped virus is inhibited from infecting the uninfected cell.


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