Nature Medicine
5, 1032 - 1038 (1999)
doi:10.1038/12469
Anti-cancer activity of targeted pro-apoptotic peptidesH. Michael Ellerby1, 2, Wadih Arap1, 4, Lisa M. Ellerby1, 2, Renate Kain1, 3, Rebecca Andrusiak1, Gabriel Del Rio1, 2, Stanislaw Krajewski1, Christian R. Lombardo1, Rammohan Rao1, 2, Erkki Ruoslahti1, Dale E. Bredesen1, 2
& Renata Pasqualini1, 41
Program on Aging and Cancer and Program on Cell Adhesion, The Burnham Institute, 10901 North Torrey Pines Rd., La Jolla, California 92037, USA 2
H.M.E., L.M.E., G.D.R., R.R. & D.E.B. present address: The Buck Center for Research in Aging, 8001 Redwood Blvd, Novato, California 94945, USA
3
R.K. present address: Clinical Institute for Clinical Pathology, Dept. Ultrastructural Pathology and Cell Biology, University of Vienna/AKH Wien, Währinger Gürtel 18-20, A-1090 Wien, Austria
4
W.A. & R.P. present address: The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, Texas 77030, USA
Correspondence should be addressed to Erkki Ruoslahti ruoslahti@burnham-inst.org or Dale E. Bredesen dbredesen@burnham-inst.org or Renata Pasqualini orpasqualini@burnham-inst.orgWe have designed short peptides composed of two functional domains, one
a tumor blood vessel 'homing' motif and the other a programmed cell death-inducing
sequence, and synthesized them by simple peptide chemistry. The 'homing' domain
was designed to guide the peptide to targeted cells and allow its internalization.
The pro-apoptotic domain was designed to be nontoxic outside cells, but toxic
when internalized into targeted cells by the disruption of mitochondrial membranes.
Although our prototypes contain only 21 and 26 residues, they were selectively
toxic to angiogenic endothelial cells and showed anti-cancer activity in mice.
This approach may yield new therapeutic agents.
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