Anti-angiogenic peptides identified in thrombospondin type I domains.
Thrombospondin 1, the prototypical protein of the thrombospondin protein family, is a potent endogenous inhibitor of angiogenesis. Although the effects of the thrombospondin 1 on neovascularization have been well studied, little is known about the anti-angiogenic potency of other proteins or peptide fragments derived from the proteins in this family. Here we identify a set of 18 novel, anti-angiogenic 17- to 20-amino acid peptides that are derived from proteins containing type I thrombospondin motifs. We have named these peptides adamtsostatin-4, adamtsostatin-16, adamtsostatin-18, cartilostatin-1, cartilostatin-2, fibulostatin-6.2, fibulostatin-6.3, papilostatin-1, papilostatin-2, properdistatin, scospondistatin, semastatin-5A.1, semastatin-5A.2, semastatin-5B, thrombostatin containing-1, thrombostatin contaning-3, thrombostatin contaning-6, and wispostatin-1 to reflect their origin. We further demonstrate that these peptides inhibit the proliferation and migration of human umbilical vein endothelial cells in vitro. The anti-proliferative and anti-migratory properties of the identified peptides may be important in maintaining angiogenic homeostasis in vivo and make these peptides suitable candidates for use as anti-angiogenic pharmaceutical agents in numerous therapeutic applications.
Karagiannis
Emmanouil D
ED
Department of Biomedical Engineering, Johns Hopkins University, School of Medicine, 613 Traylor Building, 720 Rultland Avenue, Baltimore, MD 21205, USA.
Popel
Aleksander S
AS
D020533:Angiogenesis Inhibitors / Q000008:administration & dosage*; D002465:Cell Movement / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology*; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000737:chemistry; D011414:Properdin / Q000008:administration & dosage* / Q000737:chemistry; D017434:Protein Structure, Tertiary; D019699:Thrombospondins / Q000008:administration & dosage* / Q000737:chemistry
D020533:Angiogenesis Inhibitors; D010446:Peptide Fragments; D019699:Thrombospondins; C000603977:properdistatin; D011414:Properdin