Nucleic acid molecules encoding endostatin protein and peptide fragments thereof
View Patent ↗An inhibitor of endothelial cell proliferation, capable of inhibiting angiogenesis and causing tumor regression, that is approximately 20 kDa and corresponds to a C-terminal fragment of collagen type XVIII, and methods of treating angiogenesis-related disease.
1. An isolated nucleic acid molecule that encodes an angiogenesis inhibitory peptide consisting of an amino acid sequence of an NC1 C-terminal region of a collagen molecule, wherein the collagen molecule is a collagen type XVIII or a collagen type XV molecule.
2. The nucleic acid molecule of claim 1 , wherein the collagen molecule is a collagen type XV molecule.
3. The nucleic acid molecule of claim 1 , wherein the collagen molecule is a collagen type XVIII molecule.
4. The nucleic acid molecule of claim 1 , wherein the NC1 C-terminal region begins at approximately amino acid 1105 or amino acid 1132 of a collagen type XVIII molecule.
5. The nucleic acid molecule of claim 1 , wherein the nucleic acid molecule further encodes an angiostatin protein or peptide.
6. A vector comprising the nucleic acid molecule of claim 1 operatively linked to a regulatory control element capable of expressing the nucleic acid molecule in a host cell.
7. The vector of claim 6 , wherein the host cell is a bacterial, insect, or yeast cell.
8. A pharmaceutical composition comprising the vector of claim 6 in a pharmaceutically acceptable carrier.
9. The pharmaceutical composition of claim 8 , wherein the collagen molecule is a collagen type XV molecule.
10. The pharmaceutical composition of claim 8 , wherein the collagen molecule is a collagen type XVIII molecule.
11. The pharmaceutical composition of claim 8 , wherein the NC1 C-terminal region begins at approximately amino acid 1105 or amino acid 1132 of a collagen type XVIII molecule.
12. The pharmaceutical composition of claim 8 additionally comprising a nucleic acid molecule encoding an angiostatin protein or peptide.
13. A An isolated nucleic acid molecule comprising a coding region that consists of a nucleotide sequence encoding an angiogenesis inhibitory peptide having an amino acid sequence of SEQ ID NO: 1.
14. A composition comprising a vector comprising a nucleic acid molecule comprising a coding region that consists of a nucleotide sequence encoding an angiogenesis inhibitory peptide operatively linked to a regulatory control element, the vector capable of expressing the nucleic acid molecule in a host cell, wherein the angiogenesis inhibitory peptide has the amino acid sequence of SEQ ID NO: 1.