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An antibiotic (sulfamethoxazole) stabilizes polypeptide (human serum albumin) even under extreme condition (elevated temperature)

Furkan, Mohammad, Sidddiqi, Mohammad Khursheed, Khan, Asra Nasir, Khan, Rizwan Hasan
International journal of biological macromolecules 2019 v.135 pp. 337-343
Alzheimer disease, absorbance, antibiotics, binding sites, circular dichroism spectroscopy, computer simulation, diabetes mellitus, fluorescence, human diseases, human serum albumin, ligands, polypeptides, sulfamethoxazole, temperature, therapeutics, transmission electron microscopy, turbidity
Since aggregation of protein result into number of human diseases including diabetes mellitus, Huntington's and Alzheimer's disease, etc. Hence prevention of aggregation of a polypeptide is of great clinical importance. Human serum albumin (HSA) being major transporter serum protein was studied here in order to prevent its aggregation under extreme conditions. Sulfamethoxazole (SMZ) which is an antibiotic, caused significant inhibition of aggregation which was evident by number of biophysical techniques. Molecular docking was performed to elucidate the protein ligand binding site. In the presence of SMZ decrease in ThT, ANS and RLS fluorescence intensity suggested the inhibitory potency of this antibiotic. Further resistance to increment in the absorbance of Congo red and turbidity was observed even at elevated temperature. Circular dichroism also corroborated these results in retaining its secondary structure in the presence of SMZ. Finally the formation of aggregates, visualized under transmission electron microscopy (TEM) validated the inhibitory tendency of SMZ. Also in the parallel sets we have monitored aggregation kinetics using ThT and turbidity assay and it is noteworthy that SMZ caused maximum inhibition at protein SMZ concentration ratio of 1:30 and 1:40. Our findings would set a hallmark for designing new therapeutics for untreatable protein conformational disorders.