Novel integrin binding peptides in cancer therapy

1126 We had previously reported on the discovery of novel alpha-3 integrin binding peptides through screening “one- bead one-compound” combinatorial cyclic peptide libraries with live ovarian adenocarcinoma cell lines [1]. We have shown that these ligands can be used as effective probes to image ovarian tumor xenografts both optically [2] and with positron emission tomography. Based on the results obtained from the primary and secondary library screens, we have designed and synthesized four tertiary libraries that can be used to further optimize our lead compounds. These libraries include (a) main chain modification with three diversity points, (b) side chain modification with three diversity points, (c) main chain and N-terminal modifications, and (d) N-terminal extensions with two diversity points. By using this sequential iterative screening approach with a number of different combinatorial libraries, we can rapidly probe the conformational spaces surrounding the initial lead compound. We have also identified other novel peptides from random peptide library screening which have a common motif that bind to ovarian adenocarcinomas as well as transition cell tumors. Preliminary data shows that one of these identified peptides preferentially binds to beta-1 integrin. These peptides could potentially be used as carrier to delivery radionuclides or cytotoxic drugs to the target tumor. 1. Aina, O.H., et al., Identification of novel targeting peptides for human ovarian cancer cells using “one-bead one-compound” combinatorial libraries. Mol Cancer Ther, 2005. 4(5): p. 806-13. 2. Aina, O.H., et al., Near- Infrared optical imaging of ovarian cancer xenografts with novel alpha-3 integrin binding peptide “OA02”. Molecular Imaging, 2005.