title: Peptide-Au Clusters Induced Tumor Cells Apoptosis via Targeting Glutathione Peroxidase-1: The Molecular Dynamics Assisted Experimental Studies.
abstract: The original motivation of the article is to give a systematic investigation on the protocol of combining computer simulation and accurate synthesis of serial peptide protected gold clusters for potent tumor targeting therapy. Glutathione peroxidase-1 (GPx-1) is a crucial antioxidant selenoenzyme that regulates cellular redox level, thus becomes a potential target in cancer treatment. We firstly utilize molecular dynamic (MD) simulation to rationally design and screen serial peptide-Au cluster compounds with special peptide sequences and precise gold atoms, which can recognize and bind specific domain of GPx-1 with high affinity. The theoretical simulations were further verified by the following peptide-Au clusters synthesis and GPx-1 activity suppression studies in buffer and cells, respectively. Further cytological experiments corroborated that peptide-Au clusters are promising nanoparticles inducing tumor cells apoptosis by suppressing GPx-1 activity and increasing higher cellular reactive oxygen species level to initiate tumor cell apoptosis through intrinsic mitochondrial pathway.
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.|University of Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Meiqing
authors.initials: M
authors.lastname: Liu
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. gaoliang@ihep.ac.cn.
authors.forename: Liang
authors.initials: L
authors.lastname: Gao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. linazhao@ihep.ac.cn.
authors.forename: Lina
authors.initials: L
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Jian
authors.initials: J
authors.lastname: He
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Qing
authors.initials: Q
authors.lastname: Yuan
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhang
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China.
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety, Institute of High Energy Physics, Chinese Academy of Sciences, Beijing, 100049, China. gaoxy@ihep.ac.cn.|Department of Chemistry and Chemical Engineering, Beijing University of Technology, Beijing, 100124, China. gaoxy@ihep.ac.cn.
authors.forename: Xueyun
authors.initials: X
authors.lastname: Gao
mesh_terms: D000230:Adenocarcinoma / Q000378:metabolism* / Q000628:therapy; D000595:Amino Acid Sequence; D017209:Apoptosis; D045744:Cell Line, Tumor; D005979:Glutathione Peroxidase / Q000378:metabolism*; D006801:Humans; D056004:Molecular Dynamics Simulation; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry / Q000493:pharmacokinetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D000094765:Glutathione Peroxidase GPX1
chemical_list: D010455:Peptides; D017382:Reactive Oxygen Species; D005979:Glutathione Peroxidase; D000094765:Glutathione Peroxidase GPX1; C000722067:GPX1 protein, human