Abboud Rola, Akil Mohammad, Charcosset Catherine, Greige-Gerges Hélène
Bioactive Molecules Research Group, PRASE, Doctoral School of Sciences and Technologies, Faculty of Sciences, Lebanese University, Lebanon; Laboratoire d'Automatique et de Génie des Procédés (LAGEP), UMR-CNRS 5007, Université Claude Bernard Lyon 1, CPE Lyon, Bat 308G, 43 Boulevard du 11 Novembre 1918, F-69622 Villeurbanne Cedex, France.
Kalma laboratory, Faculty of Sciences, Lebanese University, Lebanon.
Chem Phys Lipids. 2017 Oct;207(Pt B):271-278. doi: 10.1016/j.chemphyslip.2017.04.007. Epub 2017 Apr 21.
Glucocorticoids (GCs) and progesterone derivatives (PGDs) are steroid hormones with well-known biological activities. Their interaction with human serum albumin (HSA) may control their distribution. Their binding to albumin is poorly studied in literature. This paper deals with the interaction of a series of GCs (cortisol, cortisone, prednisolone, prednisone, 6-methylprednisolone and 9-fluorocortisol acetate) and PGDs (progesterone, hydroxylated PGDs, methylated PGDs and dydrogesterone) with HSA solution (pH 7.4) at molar ratios steroid to HSA varying from 0 to 10. Similar titrations were conducted using Trp aqueous solution. Fluorescence titration method and Fourier transform infrared spectroscopy (FTIR) are used. PGDs (except dydrogesterone), cortisone and 9-fluorocortisol acetate affected weakly the fluorescence of Trp in buffer solution while they decreased in a dose-dependent manner that of HSA. Their binding constants to HSA were then calculated. Moreover, displacement experiment was performed using bilirubin as a site marker. The binding constant of bilirubin to albumin was determined in the absence and presence of a steroid at a molar ratio steroid to HSA of 1. The results indicate that the steroids bind to HSA at site I in a pocket different from that of bilirubin. Furthermore, the peak positions of amide I and amide II bands of HSA were shifted in the presence of progesterone, dydrogesterone and GCs. Also a variation was observed in amide I region indicating the formation of hydrogen bonding between albumin and steroids.
糖皮质激素（GCs）和孕酮衍生物（PGDs）是具有众所周知生物活性的类固醇激素。它们与人血清白蛋白（HSA）的相互作用可能会控制其分布。文献中对它们与白蛋白的结合研究较少。本文研究了一系列糖皮质激素（皮质醇、可的松、泼尼松龙、泼尼松、6-甲基泼尼松龙和9-氟醋酸皮质醇）和孕酮衍生物（孕酮、羟基化孕酮衍生物、甲基化孕酮衍生物和地屈孕酮）与HSA溶液（pH 7.4）在类固醇与HSA的摩尔比从0到10变化时的相互作用。使用色氨酸水溶液进行了类似的滴定。采用荧光滴定法和傅里叶变换红外光谱（FTIR）。孕酮衍生物（地屈孕酮除外）、可的松和9-氟醋酸皮质醇对缓冲溶液中色氨酸的荧光影响较弱，而它们以剂量依赖性方式降低了HSA的荧光。然后计算了它们与HSA的结合常数。此外，使用胆红素作为位点标记物进行了置换实验。在类固醇与HSA的摩尔比为1的情况下，测定了胆红素在不存在和存在类固醇时与白蛋白的结合常数。结果表明，这些类固醇在与胆红素不同的口袋中的位点I与HSA结合。此外，在孕酮、地屈孕酮和糖皮质激素存在的情况下，HSA的酰胺I和酰胺II带的峰位发生了移动。在酰胺I区域也观察到了变化，表明白蛋白与类固醇之间形成了氢键。
