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Transcript 
Computational Protein Design to Reengineer Stromal Cell–
Derived Factor-1α Generates an Effective and Translatable
Angiogenic Polypeptide Analog
by William Hiesinger, Jose Manuel Perez-Aguilar, Pavan Atluri, Nicole A. Marotta,
John R. Frederick, J. Raymond Fitzpatrick, Ryan C. McCormick, Jeffrey R. Muenzer,
Elaine C. Yang, Rebecca D. Levit, Li-Jun Yuan, John W. MacArthur, Jeffery G.
Saven, and Y. Joseph Woo
Circulation
Volume 124(11 suppl 1):S18-S26
September 13, 2011
Copyright © American Heart Association, Inc. All rights reserved.
Crystallographic structures of stromal cell–derived factor-1α (SDF)27 and designed model
structure of ESA. The different regions of the structure are colored as N-terminal (green), central
region (yellow), and C-terminal (magenta).
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
Top and side view of model stromal cell–derived factor-1α (SDF) analog peptides using 1-proline
(A), 2-proline (B), and 3-proline (C) residues to link the N- and C-termini.
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
All of the residues from the ESA loop or linker region (F14, E15, S16, and L20) are located inside
favored regions in the Ramachandran plots (bounded by the blue and purple lines), which
indicate allowable bond angles.
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
Space-filling representation of the ESA and stromal cell–derived factor-1α (SDF) structures.
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
Representative images of Boyden chamber assay filters demonstrating green fluorescent
protein–positive endothelial progenitor cell (EPC) migration when exposed to a saline, stromal
cell–derived factor-1α (SDF), and ESA gradient, respectively.
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
Dose-response curve of endothelial progenitor cell (EPC) migration comparing molar equivalent
concentration gradients of ESA and stromal cell–derived factor-1α (SDF).
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
Isolated endothelial progenitor cells cultured and stimulated with either stromal cell–derived
factor-1α (A and B) or ESA (C and D) demonstrated robust and universal expression of the
chemokine receptor 4 (CXCR4 receptor; green).
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
At 2 weeks, border-zone myocardial tissue samples show increased levels of mouse
angiopoietin-1 (Ang-1) in the ESA-treated and stromal cell–derived factor-1α (SDF)–treated
groups compared with the control group.
William Hiesinger et al. Circulation. 2011;124:S18-S26
Copyright © American Heart Association, Inc. All rights reserved.
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