biological effects of a de novo designed myxoma virus peptide analogue evaluation of cytotoxicity on tumor cells生物效应的从头设计粘液瘤病毒多肽模拟评价肿瘤细胞的细胞毒性.pdf

Biological Effects of a De Novo Designed Myxoma Virus Peptide Analogue: Evaluation of Cytotoxicity on Tumor Cells 1,3 2,3 1 1 1,3 Taghrid S. Istivan *, Elena Pirogova , Emily Gan , Nahlah M. Almansour , Peter J. Coloe , Irena Cosic2,3 1 School of Applied Sciences, Science Engineering and Health College, RMIT University, Melbourne, Australia, 2 School of Electrical and Computer Engineering, Science Engineering and Health College, RMIT University, Melbourne, Australia, 3 Health Innovations Research Institute, RMIT University, Melbourne, Australia Abstract Background: The Resonant Recognition Model (RRM) is a physico-mathematical model that interprets protein sequence linear information using digital signal processing methods. In this study the RRM concept was employed for structure- function analysis of myxoma virus (MV) proteins and the design of a short bioactive therapeutic peptide with MV-like antitumor/cytotoxic activity. Methodology/Principal Findings: The analogue RRM-MV was designed by RRM as a linear 18 aa 2.3 kDa peptide. The biological activity of this computationally designed peptide analogue against cancer and normal cell lines was investigated. The cellular cytotoxicity effects were confirmed by confocal immunofluorescence microscopy, by measuring the levels of cytoplasmic lactate dehydrogenase (LDH) and by Prestoblue cell viability assay for up to 72 hours in peptide treated and non-treated cell cultures. Our results revealed that RRM-MV induced a significant dose and time-dependent cytotoxic effect on murine and human cancer cell lines. Yet, when normal murine cell lines were similarly treated with RRM-MV, no cytotoxic effects were ob