Fusion proteins comprising CD4 and the malaria parasite merozoite glycophorin binding protein 130 (GBP-130)

• US 7,585,508 B1
• Filed: 03/10/1993
• Issued: 09/08/2009
• Est. Priority Date: 03/11/1992
• Status: Active Grant

• Current Assignee: Kenneth F. Prendergast
• Original Assignee: Kenneth F. Prendergast
• Inventors: Prendergast, Kenneth F.
• Primary Examiner(s): PARKIN, JEFFREY S
• Application Number:
  US08/307,742
• Time in Patent Office: 6,026 Days
• Field of Search: 530/350, 435/172.3, 435/69.7, 536/23.4, 424/192.1, 424/272.1
• US Class Current: 424/192.1
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: C07K 14/70514 CD4
• CPC Class Codes: C07K 2319/32 fusions with soluble part of a cell surface receptor, "decoy receptors"
• CPC Class Codes: C07K 2319/33 fusions for targeting to specific cell types, e.g. tissue specific targeting, targeting of a bacterial subspecies
• CPC Class Codes: Y02A 50/30 Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

Novel hybrid fusion peptides are disclosed. The novel peptides are formed by the fusion of two or more components. One component is a peptide sequence or variant of a peptide sequence derived from a malaria parasite merozoite peptide which has affinity for and binding capability to red blood cells.

In particular segments of the glycophorin binding peptide 130 (GBP130), are preferred for the first component. Also disclosed are alternative first components, the glycophorin binding peptide homologues (GBPH), or the erythrocyte binding antigen 175 (EBA175), or the plasmodium vivax Duffy receptor or the pre major merozoite surface antigen PMMSA or the (P200) peptide.

The first component peptide is fused to all or part of a peptide segment derived from the CD4 molecule or part thereof or variant thereof which shows binding affinity for the HIV virus.

The resulting fusion peptide being exemplified as

• NH2-CD4-GBP130-COOH
• 1-371 201-774

Also disclosed are the methods of manufacture and means to use the novel hybrid peptides as clinical agents to treat, prevent or test for HIV infection.

Claims

1. A fusion protein comprising two or more components wherein the first component comprises the CD4 protein, or a substitution, deletion, or insertion analog or fragment of the CD4 protein, and the second component comprises the malaria parasite merozoite glycophorin binding protein 130 (GBP-130), or a substitution, deletion, or insertion analog or fragment of the GBP-130 protein thereof, wherein the CD4 component retains the ability to bind to the human immunodeficiency virus (HIV) envelope glycoprotein and the GBP-130 component retains the ability to bind to erythrocytes.

2. The fusion protein of claim 1, wherein the GBP-130 component is fused to the CD4 component either N- or C-terminally.

3. The fusion protein of claim 1, wherein the CD4 component is fused to the GBP component either N- or C-terminally.

4. The fusion protein of claim 1 wherein said protein comprises a linker between the first and second component.

5. The fusion protein of claim 1 wherein the fusion protein comprises amino acids 1-177 or 1-371 of CD4 fused to amino acids 201-774, 207-774, 227-774, or 370-425 of GBP-130.

6. The fusion protein according to claim 5 comprising the following formula:

NH2-CD4(1-371)-GBP-130(201-774)-COOH.

7. The fusion protein according to claim 5 comprising the following formula:

NH2-CD4(1-177)-GBP-130(201-774)-COOH.

8. The fusion protein according to claim 5 comprising the following formula:

NH2-CD4(1-177)-GBP-130(1-74)-COOH.

9. The fusion protein according to claim 1 wherein a protein fragment comprising all or part of the amino acid sequence set forth in SEQ ID NO.:

6 is inserted between the CD4 and GBP-130 components.