An Investigation on Structure and Function of The Specific Ligands of Cancerous Cells for Designing a NewGeneration of Immunotoxins

Different generations of immunotoxins could be targeting cancerous cells by interactionbetween ligand and cell surface specific antigens. Therefore, identifying and characterizationthese types of ligands and corresponding antigens, which are constantly growing, would beprovided authority to design a novel generation of immunotoxins. Bearing in mind, acomprehensive profile of cell surface specific antigens were collected, and then theexpressions of them were measured via Protegen and Proteinatlas programs on severalnormal and cancerous tissues. Corresponding ligands of the selected antigens were theninvestigated by String, and validation through docking programs including Hex, Cluspro andPatchDock. On the other hand, structural and functional characteristics and also posttranslationalmodifications of detected ligands were examined. Finally, any amino acids ofligands that are involved in interaction to antigens were determined via Pymol and Rasmolprograms. The results of this study lead to introducing some antigens including Gp75,MAGE3, APCs, PSA, and MSLN, with high expression on surface of some cancerous cells.Moreover, this investigation revealed HLA-A, ALDH3A2, MLANA, AR, CALB2, SILV, CALU,and GAGE1 as ligands with high affinity to one or more selected antigens. Meanwhile, ligandminiaturization, lead to design a new generation of ligands, with 30 amino acid in length andlimited in post-translational modification. Taken together, these results introduced a series ofcell surface specific antigens which can use for cancer diagnosis, and provide a numerous ofcandidate ligands for development a new generation of immunotoxins for targeting cancerouscells of the breast, prostate, ovary and melanoma.

کلیدواژه ها:

Cancer ، Immunotoxins ، Antigen ، Ligand ، Bioinformatics