Biomolecular study and conjugation of two para-aminobenzoic acid derivatives with serum proteins: drug binding efficacy and protein structural analysis

• Published in: Journal of biomolecular structure & dynamics 2021-01, Vol.39 (1), p.79-90
• Main Authors: Chanphai, P., Cloutier, F., Oufqir, Y., Leclerc, M.-F., Eiján, A.M., Reyes-Moreno, C., Bérubé, G., Tajmir-Riahi, H.A.
• Format: Article
• Language: English
• Subjects: binding efficacy; DAB-0; DAB-1; delivery; serum protein; thermodynamic analysis
• ISSN: 0739-1102; 1538-0254
• DOI: 10.1080/07391102.2020.1719889

Two aminobenzoic acid derivatives DAB-0 and DAB-1 showed distinct biological properties on murine bladder cancer (BCa) cell line MB49-I. In contrast to DAB-1, DAB-0 does not possess any anti-inflammatory activity and is less toxic. Furthermore, DAB-0 does not interfere with INFγ-induced STAT1 activation and TNFα-induced IκB phosphorylation, while DAB-1 does. In order to rationalize these results, the binding efficacy of DAB-0 and DAB-1 with serum proteins such a human serum albumin (HSA), bovine serum albumin (BSA) and beta-lactoglobulin (β-LG) was investigated in aqueous solution at physiological pH. Multiple spectroscopic methods and thermodynamic analysis were used to determine the binding efficacy of DAB-0 and DAB-1 with serum proteins. Drug-protein conjugation was observed via through ionic contacts. DAB-1 forms stronger adducts than DAB-0, while β-LG shows more affinity with the order of stability β-LG > BSA > HSA. The stronger complexation of DAB-1 with serum proteins might account for its biological potential and transport in the blood. The binding efficacy ranged from 40 to 60%. Major alterations of protein secondary structures were detected upon drug complexation. Serum proteins are capable of delivering DAB-1 in vitro. Communicated by Ramaswamy H. Sarma