title: Construction of novel chimeric proteins through the truncation of SEC2 and Sak from Staphylococcus aureus.
abstract: It is an usual clinical phenomenon that cancer patients are prone to thrombosis. Until now, there have been no efficient methods or appropriate drugs to prevent and cure tumor thrombus. Therefore, the construction of a bifunctional chimeric protein for the treatment of cancer, complicated with thrombosis, is of great significance. Utilizing the superantigenic activity of staphylococcal enterotoxin C2 (SEC2) and the thrombolytic activity of staphylokinase (Sak), Sak-linker-SEC2 and SEC2-linker-Sak were constructed which had good anti-tumor and thrombolytic activities at the same time. Due to the intrinsic emetic activity of SEC2 and high molecular weight (MW) of chimeric proteins (44 kDa), their clinical applications will be restricted. In this study, novel chimeric proteins including ΔSEC2-ΔSak and ΔSak-ΔSEC2 were constructed through the truncation of SEC2 and Sak without 9-Ala linker and His-tag. Compared with the former, both the truncated proteins preserved nearly the same anti-tumor and thrombolytic activities. In addition, their MWs were only 29 kDa and their immunoreactivities were slightly lower than that of Sak-linker-SEC2 and SEC2-linker-Sak, respectively. Therefore, the novel chimeric proteins possessed merits and characteristics, such as low MS, low immunogenicity, and difunctionality which the former had not. It will be of great interest if the above-mentioned proteins can be used to cure Trousseau syndrome in clinic.
authors.affiliation: a Institute of Life Science and Bio-pharmaceutics , Shenyang Pharmaceutical University , Shenyang , China.
authors.forename: Jing
authors.initials: J
authors.lastname: Hui
authors.forename: Xiao-jie
authors.initials: XJ
authors.lastname: Yu
authors.forename: Xiao-jin
authors.initials: XJ
authors.lastname: Cui
authors.forename: Teng
authors.initials: T
authors.lastname: Mu
authors.forename: Jia-shuai
authors.initials: JS
authors.lastname: Lin
authors.forename: Pei
authors.initials: P
authors.lastname: Ni
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Song
authors.initials: S
authors.lastname: You
authors.forename: Feng-qing
authors.initials: FQ
authors.lastname: Hu
mesh_terms: D004768:Enterotoxins / Q000008:administration & dosage / Q000235:genetics*; D005343:Fibrinolytic Agents / Q000008:administration & dosage; D006801:Humans; D008666:Metalloendopeptidases / Q000008:administration & dosage / Q000235:genetics*; D009369:Neoplasms / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D015202:Protein Engineering; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage* / Q000737:chemistry / Q000235:genetics; D013211:Staphylococcus aureus / Q000737:chemistry; D013927:Thrombosis / Q000150:complications / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D004768:Enterotoxins; D005343:Fibrinolytic Agents; D011993:Recombinant Fusion Proteins; C034959:enterotoxin C, staphylococcal; D008666:Metalloendopeptidases; C022653:auR protein, Staphylococcus aureus
keywords: Trousseau syndrome; anti-tumor; thrombolytic; truncated chimeric protein