Chimeric receptor binding proteins resistant to proteolytic degradation
AssigneeEligo Bioscience
InventorsJesus Fernandez Rodriguez, Xavier Duportet
Life of this patent
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Abstract
The present disclosure provides a chimeric receptor binding protein (RBP) resistant to proteolytic digestion wherein said RBP comprises a portion of a receptor binding protein derived from a bacteriophage fused through a designed linker region consisting of 1 to 70 amino acids, to a portion of a receptor binding protein derived from a different bacteriophage, wherein said linker region is designed to be resistant to proteolytic digestion.
Claims17
A chimeric receptor binding protein (RBP) resistant to proteolytic digestion,
- wherein said chimeric RBP comprises an N-terminal region of a side tail fiber (STF) protein from a lambdoid bacteriophage, fused through a designed linker region consisting of 1 to 70 amino acids or 1 to 30 amino acids, to a C-terminal region of a RBP protein from a different bacteriophage, wherein said N-terminal region and C-terminal region are fused within an insertion site of the N-terminal STF region, said insertion site, having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:
- 1), ADAKKS (SEQ ID NO:
- 2), MDETNR (SEQ ID NO:
- 3), SASAAA (SEQ ID NO:
- 4), and GAGENS (SEQ ID NO:
- 5);
- and wherein said designed linker region comprises a helix or helical bundle and wherein said linker region is resistant to proteolytic cleavage.
A chimeric receptor binding protein (RBP) resistant to proteolytic digestion,
- wherein said chimeric RBP comprises an N-terminal region of a side tail fiber (STF) protein from a lambdoid bacteriophage, fused through a designed linker region consisting of 1 to 70 amino acids or 1 to 30 amino acids, to a C-terminal region of a RBP protein from a different bacteriophage, wherein said N-terminal region and C-terminal region are fused within a site of the N-terminal STF region, called insertion site, having at least 80% identity with a site selected from the group consisting of amino acids SAGDAS (SEQ ID NO:
- 1), ADAKKS (SEQ ID NO:
- 2), MDETNR (SEQ ID NO:
- 3), SASAAA (SEQ ID NO:
- 4), and GAGENS (SEQ ID NO:
- 5);
- and
- (i) wherein said N-terminal region or said C-terminal region comprises the sequence of the linker region, said sequence being identical to the corresponding sequence in the N-terminal region or C-terminal region of the RBP from which it is derived, and said sequence restoring resistance to proteolytic digestion to said chimeric RBP compared to a chimeric RBP only differing by the absence of said linker region, and wherein said designed linker region comprises, or consists of, the amino acid sequence GSATDVMIQL (SEQ ID NO:
- 6) or GSATDVMIQLA (SEQ ID NO:
- 7);
- or
- (ii) wherein said designed linker region comprises or consists of an heterologous amino acid sequence which is not from one of the RBP from which the N-terminal region and the C-terminal region of the chimeric RBP are derived, and wherein said designed linker region comprises, or consists of, the amino acid sequence of SEQ ID NO:
- 34 or SEQ ID NO:
- 36 wherein said designed linker region comprises a helix or helical bundle and wherein said linker region is designed to be resistant to proteolytic digestion.
A chimeric receptor binding protein (RBP) resistant to proteolytic digestion, wherein said RBP comprises a portion of a receptor binding protein from a bacteriophage fused through a designed linker region consisting of 1 to 70 amino acids, to a portion of a receptor binding protein from a different bacteriophage, wherein said linker region is designed to be resistant to proteolytic digestion, wherein said chimeric RBP comprises, or consists of, the sequence of SEQ ID NO:
- 9, SEQ ID NO:
- 10, SEQ ID NO:
- 11, SEQ ID NO:
- 13, SEQ ID NO:
- 14, SEQ ID NO:
- 38 or SEQ ID NO:
- 40.
Dependencies are inferred from the claim text.