PURPOSE: YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo. RESULTS: dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments. CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types.
PURPOSE:YSA is an EphA2-targeting peptide that effectively delivers anticancer agents to prostate cancer tumors. Here, we report on how we increased the drug-like properties of this delivery system. EXPERIMENTAL DESIGN: By introducing non-natural amino acids, we have designed two new EphA2 targeting peptides: YNH, where norleucine and homoserine replace the two methionine residues of YSA, and dYNH, where a D-tyrosine replaces the L-tyrosine at the first position of the YNH peptide. We describe the details of the synthesis of YNH and dYNH paclitaxel conjugates (YNH-PTX and dYNH-PTX) and their characterization in cells and in vivo. RESULTS:dYNH-PTX showed improved stability in mouse serum and significantly reduced tumor size in a prostate cancer xenograft model and also reduced tumor vasculature in a syngeneic orthotopic allograft mouse model of renal cancer compared with vehicle or paclitaxel treatments. CONCLUSION: This study reveals that targeting EphA2 with dYNH drug conjugates could represent an effective way to deliver anticancer agents to a variety of tumor types.
Authors: Madhu Macrae; Richard M Neve; Pablo Rodriguez-Viciana; Christopher Haqq; Jennifer Yeh; Chira Chen; Joe W Gray; Frank McCormick Journal: Cancer Cell Date: 2005-08 Impact factor: 31.743
Authors: Christopher J Herrem; Tomohide Tatsumi; Kathleen S Olson; Keisuke Shirai; James H Finke; Ronald M Bukowski; Ming Zhou; Amy L Richmond; Ithaar Derweesh; Michael S Kinch; Walter J Storkus Journal: Clin Cancer Res Date: 2005-01-01 Impact factor: 12.531
Authors: X Li; V Placencio; J M Iturregui; C Uwamariya; A-R Sharif-Afshar; T Koyama; S W Hayward; N A Bhowmick Journal: Oncogene Date: 2008-08-25 Impact factor: 9.867
Authors: Benjamin D Ferguson; Maria S Tretiakova; Mark W Lingen; Parkash S Gill; Ravi Salgia Journal: Growth Factors Date: 2014-11-13 Impact factor: 2.511
Authors: Elisa Barile; Si Wang; Swadesh K Das; Roberta Noberini; Russell Dahl; John L Stebbins; Elena B Pasquale; Paul B Fisher; Maurizio Pellecchia Journal: ChemMedChem Date: 2014-03-26 Impact factor: 3.466
Authors: Bainan Wu; Si Wang; Surya K De; Elisa Barile; Bridget A Quinn; Irina Zharkikh; Angela Purves; John L Stebbins; Robert G Oshima; Paul B Fisher; Maurizio Pellecchia Journal: Chem Biol Date: 2015-07-09
Authors: Madhoosudan A Patil; Arun K Upadhyay; Laura Hernandez-Lagunas; Ryan Good; Todd C Carpenter; Carmen C Sucharov; Eva Nozik-Grayck; Uday B Kompella Journal: Artif Cells Nanomed Biotechnol Date: 2018-11-19 Impact factor: 5.678