Artemisinin Research Center, Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.
Lingnan Medical Research Center, the first Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510006, P. R. China.
Org Biomol Chem. 2022 Jun 29;20(25):5076-5085. doi: 10.1039/d2ob00717g.
Human serum albumin (HSA) can bind with numerous drugs, leading to a significant influence on drug pharmacokinetics as well as undesirable drug-drug interactions due to competitive binding. Probing the HSA drug binding site thus offers great opportunities to reveal drug-HSA binding profiles. In the present study, a fluorescent probe ()-4-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1-propylpyridin-1-ium (TTPy) has been prepared, which exhibits enhancement of deep-red to near-infrared (NIR) fluorescence upon HSA binding. The competitive binding assay indicated that TTPy can target the HSA binding site of fenamates, a group of non-steroidal anti-inflammatory drugs (NSAIDs), with moderate binding affinity (1.95 × 10 M at 303 K). More interestingly, TTPy enables fluorescent labeling of HSA upon visible light irradiation. This study provides promising ways for HSA drug binding site identification and photochemical protein labeling.
人血清白蛋白 (HSA) 可以与许多药物结合，由于竞争结合，这会对药物药代动力学产生重大影响，并导致不良的药物相互作用。因此，探测 HSA 药物结合位点为揭示药物-HSA 结合谱提供了很好的机会。在本研究中，制备了一种荧光探针 ()-4-(2-(5-(4-(二苯基氨基)苯基)噻吩-2-基)乙烯基)-1-丙基吡啶-1-翁（TTPy），其在与 HSA 结合后表现出深红光至近红外（NIR）荧光的增强。竞争性结合测定表明，TTPy 可以与非甾体抗炎药（NSAIDs）组中的芬那酸类药物靶向 HSA 结合位点，具有中等结合亲和力（在 303 K 时为 1.95×10 M）。更有趣的是，TTPy 可以在可见光照射下实现 HSA 的荧光标记。这项研究为 HSA 药物结合位点鉴定和光化学蛋白质标记提供了有前景的方法。
