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

Chung Hyun Cho; Richard A. Kammerer; Hyuek Jong Lee; Michel O. Steinmetz; Young Shin Ryu; Sung Ho Lee; Kunio Yasunaga; Kyung Tae Kim; Injune Kim; Han Ho Choi; Won Kim; Sung Hyun Kim; Sung Kwang Park; Gyun Min Lee; Gou Young Koh

doi:10.1073/pnas.0307574101

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

Chung Hyun Cho, Richard A. Kammerer, Hyuek Jong Lee, Michel O. Steinmetz, Young Shin Ryu, Sung Ho Lee, Kunio Yasunaga, Kyung Tae Kim, Injune Kim, Han Ho Choi, Won Kim, Sung Hyun Kim, Sung Kwang Park, Gyun Min Lee, Gou Young Koh

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Pages (from-to)	5547-5552
Number of pages	5
Journal	Proceedings of the National Academy of Sciences of the United States of America
Volume	101
Issue number	15
DOIs	https://doi.org/10.1073/pnas.0307574101
Publication status	Published - 13 Apr 2004

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Cho, C. H., Kammerer, R. A., Lee, H. J., Steinmetz, M. O., Ryu, Y. S., Lee, S. H., Yasunaga, K., Kim, K. T., Kim, I., Choi, H. H., Kim, W., Kim, S. H., Park, S. K., Lee, G. M., & Koh, G. Y. (2004). COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity. Proceedings of the National Academy of Sciences of the United States of America, 101(15), 5547-5552. https://doi.org/10.1073/pnas.0307574101

@article{25cdd3597d824f35af21c3b5ec66f94c,

title = "COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity",

abstract = "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.",

author = "Cho, {Chung Hyun} and Kammerer, {Richard A.} and Lee, {Hyuek Jong} and Steinmetz, {Michel O.} and Ryu, {Young Shin} and Lee, {Sung Ho} and Kunio Yasunaga and Kim, {Kyung Tae} and Injune Kim and Choi, {Han Ho} and Won Kim and Kim, {Sung Hyun} and Park, {Sung Kwang} and Lee, {Gyun Min} and Koh, {Gou Young}",

year = "2004",

month = apr,

day = "13",

doi = "10.1073/pnas.0307574101",

language = "English",

volume = "101",

pages = "5547--5552",

journal = "Proceedings of the National Academy of Sciences of the United States of America",

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Cho, CH, Kammerer, RA, Lee, HJ, Steinmetz, MO, Ryu, YS, Lee, SH, Yasunaga, K, Kim, KT, Kim, I, Choi, HH, Kim, W, Kim, SH, Park, SK, Lee, GM & Koh, GY 2004, 'COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity', Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 15, pp. 5547-5552. https://doi.org/10.1073/pnas.0307574101

TY - JOUR

T1 - COMP-Ang1: A designed angiopoietin-1 variant with nonleaky angiogenic activity

AU - Cho, Chung Hyun

AU - Kammerer, Richard A.

AU - Lee, Hyuek Jong

AU - Steinmetz, Michel O.

AU - Ryu, Young Shin

AU - Lee, Sung Ho

AU - Yasunaga, Kunio

AU - Kim, Kyung Tae

AU - Kim, Injune

AU - Choi, Han Ho

AU - Kim, Won

AU - Kim, Sung Hyun

AU - Park, Sung Kwang

AU - Lee, Gyun Min

AU - Koh, Gou Young

PY - 2004/4/13

Y1 - 2004/4/13

N2 - 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.

AB - 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.

U2 - 10.1073/pnas.0307574101

DO - 10.1073/pnas.0307574101

M3 - Article

C2 - 15060279

SN - 0027-8424

VL - 101

SP - 5547

EP - 5552

JO - Proceedings of the National Academy of Sciences of the United States of America

JF - Proceedings of the National Academy of Sciences of the United States of America

IS - 15

ER -

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

Abstract

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