Truncated cystine-knot proteins
AssigneesPepscan Systems B.V., Universiteit Maastricht, Academisch Ziekenhuis Maastricht
InventorsPeter Timmerman, Wouter C. Puijk, Tilman M. Hackeng, Arjan W. Griffioen
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Abstract
The invention relates to the fields of protein chemistry, biology and medicine. More specifically, it relates to the design and preparation of proteinmimics of members of the cystine-knot growth factor superfamily. Further, the invention relates to the use of these proteinmimics as a medicament or prophylactic agent. The invention provides proteinmimics of members of the cystine-knot growth factor superfamily, preferably for use in immunogenic and/or therapeutic compositions.
Claims12
A proteinmimic of a member of the cystine-knot growth factor superfamily, wherein the proteinmimic comprises a motif
- X0-C1-X1-C2-X2-C3-X3-C4-X4-C5-X5-C6-X6 (SEQ ID NO:2),
- wherein C1 to C6 are cysteine residues that form a cystine-knot structure in which C1 is linked to C4, C2 is linked to C5, and C3 is linked to C6,
- wherein
- X0 comprises KFMDVYQRSY (amino acids 1-10 of SEQ ID NO:12),
- X1 comprises HPIETLVDIFQEYPDEIEYIFKPSAVPLMR (amino acids 2-31 of SEQ ID NO:27),
- X2 comprises GGA,
- X3 comprises NDEGLE (amino acids 37-42 of SEQ ID NO:27),
- X4 comprises VPTEESNITMQIMRIKPHQGQHIGEMSFLQHNK (amino acids 44-76 of SEQ ID NO:27),
- X5 comprises E, and
- X6 comprises RPKKDRARQE (amino acids 90-99 of SEQ ID NO:12),
- or wherein said protein mimic consists of a sequence having at least 95% sequence identity to SEQ ID NO:27;
- wherein said protein mimic comprises the consensus sequence P[PSR]CVXXXRC2[GSTA]GCC3 (SEQ ID NO:5) wherein at least one cysteine, other than C2 or C3, is replaced by another amino acid residue and wherein X means any amino acid, [PSR] means P or S or R and [GSTA] means G or S or T or A.
A proteinmimic member of the cystine-knot growth factor superfamily, wherein said member of the cystine-knot growth factor superfamily is placental growth factor (PLGF), and wherein said proteinmimic consists of SEQ ID NO:14.
A proteinmimic of a member of the cystine-knot growth factor superfamily, wherein said member is sclerostin, and wherein said proteinmimic consists of SEQ ID NO:31.
A proteinmimic of a member of the cystine-knot growth factor superfamily, wherein the proteinmimic consists of SEQ ID NO:35.
A proteinmimic of human Vascular Endothelial Growth Factor (hVEGF), wherein the proteinmimic comprises a motif
- X0-C1-X1-C2-X2-C3-X3-C4-X4-C5-X5-C6-X6 (SEQ ID NO:2),
- wherein C1 to C6 are cysteine residues that form a cystine-knot structure in which C1 is linked to C4, C2 is linked to C5, and C3 is linked to C6,
- wherein X0 comprises KFMDVYQRSY (amino acids 1-10 of SEQ ID NO:12), X1 comprises HPIETLVDIFQEYPDEIEYIFKPSAVPLMR (amino acids 2-31 of SEQ ID NO:27), X2 comprises GGA, X3 comprises NDEGLE (amino acids 47-52 of SEQ ID NO:12), X4 comprises VPTEESNITMQIMRIKPHQGQHIGEMSFLQHNK (amino acids 54-86 of SEQ ID NO:12), X5 comprises E, and X6 comprises RPKKDRARQE (amino acids 47-52 of SEQ ID NO:12).
A proteinmimic of human Vascular Endothelial Growth Factor (hVEGF), wherein the proteinmimic comprises a motif
- C1-X1-C2-X2-C3-X3-C4-X4-C5-X5-C6 (SEQ ID NO:2),
- wherein C1 to C6 are cysteine residues that form a cystine-knot structure in which C1 is linked to C4, C2 is linked to C5, and C3 is linked to C6,
- wherein X1 comprises HPIETLVDIFQEYPDEIEYIFKPSAVPLMR (amino acids 2-31 of SEQ ID NO:27), X2 comprises GGA, X3 comprises NDEGLE (amino acids 37-42 of SEQ ID NO:27), X4 comprises VPTEESNITMQIMRIKPHQGQHIGEMSFLQHNK (amino acids 44-76 of SEQ ID NO:27), and X5 comprises E.
Dependencies are inferred from the claim text.