caa a22 4500 445326417 CHVBK 20180317142722.0 cr unu---uuuuu 170323e20110901xx s 000 0 eng 10.1007/s10989-011-9265-9 doi (NATIONALLICENCE)springer-10.1007/s10989-011-9265-9 Small Azurin Derived Peptide Targets Ephrin Receptors for Radiotherapy [Elektronische Daten] [Ewa Micewicz, Chun-Ling Jung, Dorthe Schaue, Hai Luong, William McBride, Piotr Ruchala] Many lung cancer treatment regimens include radiotherapy. We sought to improve the efficacy of such treatment by invoking the targeted delivery of a model radiosensitizer (nicotinamide) to malignant tissues. Ephrin receptors (Eph), which are often overexpressed in lung cancers, were selected as the target of our delivery system. Molecular targeting was achieved utilizing a small peptide derived from the C-terminal portion of azurin, a copper-containing redox protein ("cupredoxin”) that is capable of binding to ephrin receptors. We prepared and screened a sub-library of peptides derived from the C-terminal region of azurin and found several small analogues that bound ephrin receptors EphA2, EphB2, and EphB4. One such peptide, termed AzV36, was selected for conjugation with nicotinic acid via an amide bond to form AzV36-NicL. The resulting linear peptide contains 15 residues (including unusual and d-amino acids), is very stable in human serum, and can be easily manufactured. AzV36-NicL conjugate was tested in vivo for its ability to radiosensitize Lewis lung carcinoma (LCC) in artificial metastasis and solid tumor engraftment models. The compound increased the efficacy of radiotherapy with tumor colonies being ~2-13 fold lower than with radiation alone depending on experimental schedule. In contrast, equimolar amounts of unconjugated peptide (AzV36-L) or nicotinamide alone only marginally improved radiation efficacy. The targeted delivery of radiosensitizer(s) to ephrin receptors may enhance the efficacy of radiation treatment of lung cancer and of other cancers that overexpress ephrin receptor(s). Springer Science+Business Media, LLC, 2011 Peptides nationallicence Ephrin receptors nationallicence Targeted radiotherapeutics nationallicence Lewis lung carcinoma nationallicence Cancer radiotherapy nationallicence Artificial metastasis nationallicence Micewicz Ewa Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut Jung Chun-Ling Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut Schaue Dorthe Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut Luong Hai Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut McBride William Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut Ruchala Piotr Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut International Journal of Peptide Research and Therapeutics Springer Netherlands 17/3(2011-09-01), 247-257 1573-3149 17:3<247 2011 17 10989 https://doi.org/10.1007/s10989-011-9265-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10989-011-9265-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Micewicz Ewa Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Jung Chun-Ling Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Schaue Dorthe Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Luong Hai Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- McBride William Department of Radiation Oncology, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 700 1- Ruchala Piotr Division of Infectious Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, University of California at Los Angeles, 10833 Le Conte Avenue, 90095, Los Angeles, CA, USA aut NATIONALLICENCE 773 0- International Journal of Peptide Research and Therapeutics Springer Netherlands 17/3(2011-09-01), 247-257 1573-3149 17:3<247 2011 17 10989 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer