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1.
In Silico Pharmacol ; 10(1): 6, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35369404

RESUMO

Anti-CD20 antibodies such as ofatumumab has demonstrated efficacy in relapsed/refractory chronic lymphocytic leukemia, are among the most successful therapies to date. In this study, we have designed an immunotoxin composed of Granzyme B and the high affinity variant of Ofatumumab. Different simulation software applied to explore the structure of Granzyme B, a serine protease in cytotoxic lymphocytes granules as an apoptosis mediator was attached to its specific antibody structure (Ofatumumab) via an adaptor sequence. The accuracy, energy minimization and characterization of biological properties of the final structure were evaluated. Our computational outcomes indicated that the employed method for structure prediction has been successfully managed to design the immunotoxin structure. The precise and accurate design of the immune-therapeutic agents against cancer cells can be confirmed by employment of in-silico approaches. Consequently, based on this approach we could introduce a capable immunotoxin which specifically targeting CD20 in an accurate orientation and initiates cancer cell destruction by its toxin domain. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-022-00120-6.

2.
Int J Pept Res Ther ; 27(4): 2417-2437, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34483787

RESUMO

Acinetobacter baumannii is one of the most successful pathogens causing nosocomial infections and has significantly multidrug-resistant. So far, there are no certain treatments to protect against infection with A. baumannii, therefore an effective A. baumannii vaccine needed. The purpose of this study was to predict antigenic epitopes of CarO protein for designing the A. baumannii vaccine using immunoinformatics analysis. CarO protein is one of the most important factors in the resistance against the antibiotic Carbapenem. In this study, T and B-cell epitopes of CarO protein were predicted and screened based on the antigenicity, toxicity, allergenicity features. The epitopes were linked by suitable linkers. Four different adjuvants were attached to the vaccine constructs which among them, vaccine construct 3 was chosen to predict the secondary and the 3D structure of the vaccine. The refinement process was performed to improve the quality of the 3D model structure; the validation process is performed using the Ramachandran plot and ProSA z-score. The designed vaccine's binding affinity to six various HLA molecules and TLR 2 and TLR4 were evaluated by molecular docking. Finally, in silico gene cloning was performed in the pET28a (+) vector. The findings suggest that the vaccine may be a promising vaccine to prevent A. baumannii infection.

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