The current strategies for targeting prostate cancer (Pca) suffer from major limitations to differentiate between benign hyperplasia and aggressive PCa. The reported peptide CTVRTSADC, which targets extra domain-B of fibronectin (EDB-Fn) in the extracellular matrix (ECM), differentiates between benign and aggressive forms. We synthesized a conjugate of EDB-Fn peptide and an anticancer drug connected through a hydrolyzable linker for potential targeted therapy of PCa. The peptide was synthesized by Fmoc/t-Bu solid phase methodology. The EDB-Fn peptide sequence was assembled followed by incorporation of spacer and cathepsin B sensitive dipeptide linker. The Boc-hydrazine group was added at the <i>N</i>–terminal for drug conjugation. The peptide was cleaved and purified by using reverse-phase high-pressure liquid chromatography and characterized using MALDI mass spectrometry. Doxorubicin was conjugated by reacting with the peptide in an acidic solution of methanol. The final disulfide cyclization was carried out between two cysteine residues in the presence of DMSO/H<sub>2</sub>O.

Design and synthesis of fibronectin-targeted peptide anticancer drug conjugates for targeted chemotherapy of prostate cancer

253rd National Meeting (2017)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.