Typical endocrine disruptors diethylstilbestrol and its analogues non-covalently bind to human serum albumin

Endocrine disruptors have received widespread attention from the scientific community. However, the structureactivity relationship of the binding between endocrine disruptors and proteins is still unclear. Therefore, this study investigated the structure-activity relationship between human serum albumin (HSA) and three types of estrogens, hexestrol (HX), diethylstilbestrol (DES), and dienestrol (DIS), which have slightly different structures. The binding constants of HX, DES and DIS with HSA at 298 K were 1.40x10(4), 3.84x10(4) and 4.46x10(4) M-1, respectively. The data of thermodynamic parameters confirmed that the entropy and enthalpy of the estrogens with HSA were positive, indicating that the binding was dominated by hydrophobic interaction. The results from photochemistry and electrochemistry showed that the binding of estrogens to HSA was more tightly regulated by the conjugation effect. The conjugation effect not only changed the binding behavior of estrogen to HSA, but also the selectivity of the binding sites of the three estrogens. These changes caused the main binding sites to become different, while also affecting the local conformation of HSA. This article provides theoretical guidance for predicting the biological safety of analogues of endocrine disruptors at the protein level.