Design, Synthesis and Structure-Activity Relationship Analysis of Charged Biotinylated Arg-Gly-Asp Derivatives against MDA-MB-231 Cells

Bonaventure M, Shoufia J, Hemamalini V, Sivasamy R and Suja S

Department of Biochemistry, Bharathiar University, Coimbatore, India
Department of Bioinformatics, Bharathiar University, Coimbatore, India
Department of Human Genetics & Molecular Biology, Bharathiar University, Coimbatore, India

^*Correspondance to: Suja Samiappan 

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Abstract:

Various studies have been done successfully to show the electrostatic interactions of charged biomolecules against the cancer cell surface but few have analyzed the effect of these electrostatic interactions on the ligand-receptor interactions. In this study, negatively charged N-Biotin-RGD and positively charged C-Biotin-RGD were designed, synthesized, and characterized with docking analysis. The fixation of MDA-MB-231 cells with formalin made their cell surface neutrally charged thus removing the electrostatic interactions between charged biotinylated RGD derivatives and MDA-MB-231 cells. The results of the binding affinity of biotinylated RGD derivatives against MDA-MB-231 cells showed that N-Biotin-RGD had higher binding affinity than C-Biotin-RGD. The cytotoxic effect was analyzed by incubating charged biotinylated RGD derivatives with live MDA-MB-231 cells. MDA-MB-231 cell surface is negatively charged due to high Hypersialylation of polyglycan and Warburg effect. The results of their cytotoxic activities against live MDA-MB-231 cells were found to be electrostatic in nature. C-Biotin-RGD had an attractive interaction with the MDA-MB-231 cell surface resulting in a higher cytotoxic effect. In comparison, N-Biotin-RGD had a repulsive interaction with the MDA-MB-231 cell surface resulting in a lower cytotoxic effect. Hence, positively charged C-Biotin-RGD is a better cytotoxic agent than a negatively charged N-Biotin-RGD against MDA-MB-231 cells.

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Cite the Article:

Bonaventure M, Shoufia J, Hemamalini V, Sivasamy R, Suja S. Design, Synthesis and Structure-Activity Relationship Analysis of Charged Biotinylated Arg-Gly-Asp Derivatives against MDA-MB-231 Cells. Clin Oncol. 2023;8:2015..