1. Biomolecular study and conjugation of two para-aminobenzoic acid derivatives with serum proteins: drug binding efficacy and protein structural analysis.
- Author
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Chanphai P, Cloutier F, Oufqir Y, Leclerc MF, Eiján AM, Reyes-Moreno C, Bérubé G, and Tajmir-Riahi HA
- Subjects
- Animals, Humans, Lactoglobulins metabolism, Mice, Protein Binding, Serum Albumin, Bovine metabolism, Serum Albumin, Human, 4-Aminobenzoic Acid, Pharmaceutical Preparations
- Abstract
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.
- Published
- 2021
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