COMP-Ang1: a designed angiopoietin-1 variant with nonleaky angiogenic activity

CH Cho, RA Kammerer, HJ Lee… - Proceedings of the …, 2004 - National Acad Sciences
CH Cho, RA Kammerer, HJ Lee, MO Steinmetz, YS Ryu, SH Lee, K Yasunaga, KT Kim, I Kim
Proceedings of the National Academy of Sciences, 2004National Acad Sciences
Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis,
enhancing endothelial cell survival, and preventing vascular leakage. However, production
of Ang1 is hindered by aggregation and insolubility resulting from disulfide-linked higher-
order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil
domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable,
and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in …
Angiopoietin-1 (Ang1) has potential therapeutic applications in inducing angiogenesis, enhancing endothelial cell survival, and preventing vascular leakage. However, production of Ang1 is hindered by aggregation and insolubility resulting from disulfide-linked higher-order structures. Here, by replacing the N-terminal portion of Ang1 with the short coiled-coil domain of cartilage oligomeric matrix protein (COMP), we have generated a soluble, stable, and potent Ang1 variant, COMP-Ang1. This variant is more potent than native Ang1 in phosphorylating the tyrosine kinase with Ig and epidermal growth factor homology domain 2 (Tie2) receptor and Akt in primary cultured endothelial cells, enhancing angiogenesis in vitro and increasing adult angiogenesis in vivo. Thus, COMP-Ang1 is an effective alternative to native Ang1 for therapeutic angiogenesis in vivo.
National Acad Sciences