ABSTRACT
Gene fragments derived from structural domains mediating physical interactions can modulate biological functions. Utilizing this, we developed lentiviral overexpression libraries of peptides comprehensively tiling high-confidence cancer driver genes. Toward inhibiting cancer growth, we assayed ~66,000 peptides, tiling 65 cancer drivers and 579 mutant alleles. Pooled fitness screens in two breast cancer cell lines revealed peptides, which selectively reduced cellular proliferation, implicating oncogenic protein domains important for cell fitness. Coupling of cell-penetrating motifs to these peptides enabled drug-like function, with peptides derived from EGFR and RAF1 inhibiting cell growth at IC50s of 27-63 µM. We anticipate that this peptide-tiling (PepTile) approach will enable rapid de novo mapping of bioactive protein domains and associated interfering peptides.
Subject(s)
Neoplasms , Cell Proliferation , Humans , Neoplasms/drug therapy , Neoplasms/genetics , Oncogenes , Peptides/chemistry , Peptides/pharmacology , Protein DomainsABSTRACT
A sol-gel method is employed for preparing high quality lead-free glass-ceramic samples (1 - x)BCZT-xBBS-incorporating Ba0.85Ca0.15Zr0.1Ti0.9O3 (BCZT) powder and Bi2O3-B2O3-SiO2 (BBS) glass-doped additives with different values of x (x = 0, 0.05, 0.1, 0.15). Systematic investigations are performed to comprehend the structural, dielectric and energy storage characteristics using X-ray diffraction, field-emission scanning electron microscopy, impedance and ferroelectric analyser methods. With appropriate BBS doping (x), many fundamental traits including breakdown strength, dielectric loss and energy storage density have shown significant improvements. Low doping-level samples x < 0.1 have retained the pure perovskite phase while a second glass phase appeared in samples with x ≥ 0.1. As the doping level (0.1 ≥ x > 0) is increased, the average grain size decreased to become better homogeneous materials with improved breakdown energy strengths. Excessive addition of BBS (x = 0.15) causes negative effects on microstructures and other traits. The glass-ceramic sample 0.95BCZT-0.05BBS exhibits excellent dielectric permittivity and temperature stability, with the highest energy storage density of 0.3907 J cm-3 at 130 kV cm-1. These results provide good reference to develop lead-free ceramics of high energy storage density.