Identification of novel short peptides derived from the α4, α5, and α6 fibrils of type IV collagen with anti-angiogenic properties

• DOI: 10.1016/j.bbrc.2006.12.231
• Publication Date: 2007-01-17T12:19:43Z
• Authors: Emmanouil D. Kara...; Aleksander S. Popel
• Keywords: Collagen Type IV; 0303 health sciences; Neovascularization, Pathologic; Molecular Sequence Data; Endothelial Cells; Angiogenesis Inhibitors; Peptide Fragments; 3. Good health; Structure-Activity Relationship; 03 medical and health sciences; Humans; Amino Acid Sequence; Endothelium, Vascular; Cells, Cultured; Cell Proliferation

Angiogenesis, or neovascularization, is tightly controlled by positive and negative regulators, many of which reside in the extracellular matrix. We have now identified eight novel 19- to 20-residue peptides derived from the alpha4, alpha5, and alpha6 fibrils of type IV collagen, which we have designated tetrastatins, pentastatins, and hexastatins, respectively. We have shown that these endogenous peptides suppress the proliferation and migration of HUVECs in vitro. By performing clustering analyses of the sequences using sequence similarity criteria and of the experimental results using a hierarchical algorithm, we report that the clusters identified by the experimental results coincide with the sequence-based clusters, indicating a tight relationship between peptide sequence and anti-angiogenic potency. These peptides may have potential as anti-angiogenic therapeutic agents.