Functional Studies on a Novel Engineered Peptide Derived from C-Terminal of Human Endostatin

Document Type: Article

Authors

1 Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran

2 Department of Biology, Faculty of Sciences, University of Guilan, Rasht, Iran

3 Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran

Abstract

Endostatin, the C-terminal fragment of collagen XVIII, is known as an endogenous inhibitor of angiogenesis and is currently used as an anticancer drug. Endostatin fragments can be used as alternatives for full-length molecule, among which a peptide derived from the C-terminal fragment of protein, including residues 123-184 was shown to effectively inhibit angiogenesis and tumor growth. The aim of current study was to design a shortened peptide of the fragment 123-184. For this purpose, the presumably non-functional segments were deleted, including β-hairpin segment, comprising residues 145-163 and C-terminus of the protein, including residues 175-184. The designed 30-amino acid peptide that encompasses random coils in 123-184 (referred to as C-peptide) was synthesized and characterized. C-peptide inhibited the proliferation of the Human Umbilical Vein Endothelial Cells (HUVECs) with an IC50 value of 0.35 µM. Administration of C-peptide caused the regression of 4T1 murine mammary carcinoma tumor growth, considerable reduced tumor cell proliferation (Ki67 expression) and angiogenesis (CD31 and CD34 expression), and the induction of apoptosis (increased TUNEL staining). These results confirm that the random coils of the C-terminal domain of endostatin are implicated in its antiangiogenic and antitumor properties.

Graphical Abstract

Functional Studies on a Novel Engineered Peptide Derived from C-Terminal of Human Endostatin

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