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Replies to post #238156 on Avid Bioservices Inc (CDMO)
cheynew
10/08/15 6:29 PM
#238157 RE: biopharm #238156
biopharm
10/28/15 9:19 PM
#240704 RE: biopharm #238156
Unbiased Selection of Peptide–Peptoid Hybrids Specific for Lung Cancer Compared to Normal Lung Epithelial Cells Jaya M. Matharage†, https://www.linkedin.com/pub/jaya-matharage/60/617/227 John D. Minna‡§?#, http://www.researchgate.net/profile/John_Minna3 Rolf A. Brekken‡§??, and http://www.researchgate.net/profile/Rolf_Brekken D. Gomika Udugamasooriya*†‡? http://www.researchgate.net/profile/Gomika_Udugamasooriya †Advanced Imaging Research Center, ‡Simmons Comprehensive Cancer Center, §Hamon Center for Therapeutic Oncology Research, ?Departments of Biochemistry, ?Pharmacology, #Internal Medicine, and ?Surgery, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, Texas 75390, United States ACS Chem. Biol., Article ASAP DOI: 10.1021/acschembio.5b00592 Publication Date (Web): October 28, 2015 Copyright © 2015 American Chemical Society To develop widely applicable diagnostic and potentially therapeutic approaches overcoming protein heterogeneity in human cancer, we have developed a technology to unbiasedly select high specificity compound(s) that bind any biomolecule (e.g., proteins, lipids, carbohydrates) presented on the cancer cell surface but not on normal cells. We utilized a peptidomimetic based on-bead two-color (OBTC) combinatorial cell screen that can detect differences between two cell surfaces at high accuracy by looking for beads (where each bead in the library had one peptide–peptoid hybrid on the surface) that only bound cancer but not normal cells. We screened a library of 393?216 compounds targeting HCC4017 lung adenocarcinoma cells (labeled in red) in the presence of HBEC30KT normal bronchial epithelial cells (labeled in green) derived from the same tissue of the same patient. This screen identified a peptide–peptoid hybrid called PPS1 which displayed high specific binding for HCC4017 cancer cells over HBEC30KT cells. Specificity was validated through on-bead, ELISA-like and magnetic bead pulldown studies, while a scrambled version of PPS1 did not show any binding. Of interest, the simple dimeric version (PPS1D1) displayed cytotoxic activity on HCC4017 cells, but not on normal HBEC30KT cells. PPS1D1 also strongly accumulated in HCC4017 lung cancer xenografts in mice over control constructs. We conclude that such combinatorial screens using tumor and normal cells from the same patient have significant potential to develop new reagents for cancer biology, diagnosis, and potentially therapy. http://pubs.acs.org/doi/abs/10.1021/acschembio.5b00592