A new approach, in vivo selection of peptide motifs from phage display libraries for peptides that home specifically to the vasculature of individual tissues or tumors, was developed by the applicant. Homing peptides for the vasculature of a large number of normal tissues and for tumor vasculature have been identify by using this method. Progress has been made recently in identifying some of the molecules (""""""""receptors"""""""") recognized by the homing peptides. The receptors for tumor-homing peptides have been shown to be markers of angiogenic vasculature, and the receptor for a peptide that homes specifically to lung vasculature has been identified. Recent screens have revealed a number of additional tumor-homing peptides for which the receptors remain to be identified. Recent screens have revealed a number of additional tumor-homing peptides for which the receptors remain to be identified. Preliminary results suggest that the tissue-specific vascular markers are lost as blood vessels grow into tumors, while the growing vessels acquire angiogenic markers. The lung-specific peptide receptor serves as a docking site for metastasizing tumor cells in the lung vasculature. The purpose of the research proposed in this component is to identify the receptors for peptides that home to pancreas and prostate vasculature, and to study the expression of the receptors for the various peptides during tumor development. Finally, the tumor cell protein that is responsible fore the binding of the cells to the homing peptide receptor in lung vasculature will be identified. This study will provide new insights to vascular specialization in normal tissues and tumors. New tools for the targeting of therapies will also result from this work.
| Duggineni, Srinivas; Mitra, Sayantan; Lamberto, Ilaria et al. (2013) Design and Synthesis of Potent Bivalent Peptide Agonists Targeting the EphA2 Receptor. ACS Med Chem Lett 4: |
| Mitra, Sayantan; Duggineni, Srinivas; Koolpe, Mitchell et al. (2010) Structure-activity relationship analysis of peptides targeting the EphA2 receptor. Biochemistry 49:6687-95 |
| Järvinen, Tero A H; Ruoslahti, Erkki (2010) Target-seeking antifibrotic compound enhances wound healing and suppresses scar formation in mice. Proc Natl Acad Sci U S A 107:21671-6 |
| Richardson, Robyn D; Ma, Gil; Oyola, Yatsandra et al. (2008) Synthesis of novel beta-lactone inhibitors of fatty acid synthase. J Med Chem 51:5285-96 |
| Jarvinen, Tero A H; Ruoslahti, Erkki (2007) Molecular changes in the vasculature of injured tissues. Am J Pathol 171:702-11 |
| Zhang, Lianglin; Giraudo, Enrico; Hoffman, Jason A et al. (2006) Lymphatic zip codes in premalignant lesions and tumors. Cancer Res 66:5696-706 |
| Browne, Cecille D; Hindmarsh, Elizabeth J; Smith, Jeffrey W (2006) Inhibition of endothelial cell proliferation and angiogenesis by orlistat, a fatty acid synthase inhibitor. FASEB J 20:2027-35 |
| Koolpe, Mitchell; Burgess, Rosemary; Dail, Monique et al. (2005) EphB receptor-binding peptides identified by phage display enable design of an antagonist with ephrin-like affinity. J Biol Chem 280:17301-11 |
| Pai, Jih-Tung; Ruoslahti, Erkki (2005) Identification of endothelial genes up-regulated in vivo. Gene 347:21-33 |
| Zhang, Lianglin; Hoffman, Jason A; Ruoslahti, Erkki (2005) Molecular profiling of heart endothelial cells. Circulation 112:1601-11 |
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