Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia.
Int J Mol Sci. 2023 Feb 24;24(5):4485. doi: 10.3390/ijms24054485.
This study demonstrates that sterigmatocystin (STC) interacts non-covalently with various cyclodextrins (CDs), showing the highest binding affinity for sugammadex (a γ-CD derivative) and γ-CD, and an almost order of magnitude lower affinity for β-CD. This difference in affinity was studied using molecular modelling and fluorescence spectroscopy, which demonstrated a better insertion of STC into larger CDs. In parallel, we showed that STC binds to human serum albumin (HSA) (a blood protein known for its role as a transporter of small molecules) with an almost two order of magnitude lower affinity compared to sugammadex and γ-CD. Competitive fluorescence experiments clearly demonstrated an efficient displacement of STC from the STC-HSA complex by cyclodextrins. These results are a proof-of-concept that CDs can be used to complex STC and related mycotoxins. Similarly, as sugammadex extracts neuromuscular relaxants (e.g., rocuronium and vecuronium) from blood and blocks their bioactivity, it could also be used as first aid upon acute intoxication to encapsulate a larger part of the STC mycotoxin from serum albumin.
本研究表明,杂色曲菌素(STC)与各种环糊精(CDs)非共价相互作用,对琥乙红霉素(γ-CD 衍生物)和 γ-CD 表现出最高的结合亲和力,对 β-CD 的亲和力几乎低一个数量级。使用分子建模和荧光光谱法研究了这种亲和力差异,结果表明 STC 更好地插入到大的 CDs 中。同时,我们表明 STC 与人血清白蛋白(HSA)(一种以作为小分子转运蛋白而闻名的血液蛋白)的结合亲和力比琥乙红霉素和 γ-CD 低近两个数量级。竞争性荧光实验清楚地表明,环糊精可以有效地将 STC 从 STC-HSA 复合物中置换出来。这些结果证明了 CD 可以用于络合 STC 和相关的霉菌毒素。类似地,由于琥乙红霉素从血液中提取神经肌肉松弛剂(如罗库溴铵和维库溴铵)并阻断其生物活性,它也可以在急性中毒时用作急救措施,将血清白蛋白中更大比例的 STC 霉菌毒素包裹起来。