Author/Authors :
taheri-anganeh, mortaza shiraz university of medical sciences - school of advanced medical sciences and technologies - department of medical biotechnology, shiraz, iran , savardashtaki, amir shiraz university of medical sciences - school of advanced medical sciences and technologies, pharmaceutical sciences research center - department of medical biotechnology, shiraz, iran , vafadar, asma shiraz university of medical sciences - school of advanced medical sciences and technologies - department of medical biotechnology, shiraz, iran , movahedpour, ahmad shiraz university of medical sciences - school of advanced medical sciences and technologies, student research committee - department of medical biotechnology, shiraz, iran , shabaninejad, zahra shiraz university of medical sciences - pharmaceutical sciences research center, shiraz, iran , shabaninejad, zahra tarbiat modares university - school of biological sciences - department of nanobiotechnology, tehran, iran , maleksabet, amir mazandaran university of medical sciences - school of advanced technologies in medicine - department of medical biotechnology, sari, iran , amiri, ahmad shiraz university of medical sciences - school of medicine - department of biochemistry, shiraz, iran , ghasemi, younes shiraz university of medical sciences - school of advanced medical sciences and technologies, pharmaceutical sciences research center , school of pharmacy - department of medical biotechnology, department of pharmaceutical biotechnology, shiraz, iran , irajie, cambyz shiraz university of medical sciences - school of advanced medical sciences and technologies - department of medical biotechnology, shiraz, iran
Abstract :
background: the most prevalent cancer in women over the world is breast cancer. immunotherapy is a promising method to effectively treat cancer patients. among various immunotherapy methods, tumor antigens stimulate the immune system to eradicate cancer cells. preferentially expressed antigen in melanoma (prame) is mainly overexpressed in breast cancer cells, and has no expression in normal tissues. flicδd2d3, as truncated flagellin (flic), is an effective toll-like receptor 5 (tlr5) agonist with lower inflammatory responses. the objective of the present study was to utilize bioinformatics methods to design a chimeric protein against breast cancer. methods: the physicochemical properties, solubility, and secondary structures of prame+flicδd2d3 were predicted using the tools protparam, protein-sol, and gor iv, respectively. the 3d structure of the chimeric protein was built using i-tasser and refined with galaxyrefine, rampage, and procheck. antigenpro and vaxijen were used to evaluate protein antigenicity, and allergenicity was checked using algpred and allergen fp. major histocompatibility complex )mhc( and cytotoxic t-lymphocytes )ctl( binding peptides were predicted using hlapred and ctlpred. finally, b-cell continuous and discontinuous epitopes were predicted using abcpred and ellipro, respectively. results: the stability and solubility of prame+flicδd2d3 were analyzed, and its secondary and tertiary structures were predicted. the results showed that the derived peptides could bind to mhcs and ctls. the designed chimeric protein possessed both linear and conformational epitopes with a high binding affinity to b-cell epitopes. conclusion: prame+flicδd2d3 is a stable and soluble chimeric protein that can stimulate humoral and cellular immunity. the obtained results can be utilized for the development of an experimental vaccine against breast cancer.
