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Paper Details

A Study on the Mechanism of Aggregation of Therapeutic Reteplase Protein by Using the Monomer-Loss Model

Soheyla Ershadi, Hamid Rashedi, Ahmad Fazeli

Journal Title:Journal of Applied Biotechnology Reports
Abstract


Aggregation of pharmaceutical proteins reduces the efficiency and increases the cost of production. It can also lead to the reduced efficacy of drug or cause side effects on the patients body. Investigating how to create them plays an important role to find agents that prevents the aggregation. This study was allocated for understanding the mechanism of formation of the reteplase protein using thermal stimulation. Aggregation was studied by ultraviolet spectrometry, and observation at 4, 25, 50 and 70C, the concentration of protein monomer was measured by using a spectrum of 360 nm and 280 nm. At 4C, there was no significant change in monomer concentration for a month. By increasing the temperature to 25?C, aggregation process was slow, but at 70C, the reaction was carried out at a rapid rate less than 2 hours. In order to investigate the mechanism of reteplase aggregation, some kinetics that was presented in of monomer-loss models were used. Experimental data was fitted in three pre balance core, self-catalytic and slow start models using MATLAB. The best fit was obtained using optimization methods. Best fit for self-catalytic model is (R2> 0.98). For other two models (R2

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