Cyclodextrin-Based Displacement Strategy of Sterigmatocystin from Serum Albumin as a Novel Approach for Acute Poisoning Detoxification

Author:

Jakšić Daniela1ORCID,Šegvić Klarić Maja1ORCID,Rimac Hrvoje2ORCID,Kerep Robert3,Piantanida Ivo4ORCID

Affiliation:

1. Department of Microbiology, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

2. Department of Medicinal Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

3. Department of General and Inorganic Chemistry, Faculty of Pharmacy and Biochemistry, University of Zagreb, 10000 Zagreb, Croatia

4. Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička Cesta 54, 10000 Zagreb, Croatia

Abstract

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.

Funder

Croatian Science Foundation

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

Reference39 articles.

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4. Fungi and their secondary metabolites in water-damaged indoors after a major flood event in eastern Croatia;Kifer;Indoor Air,2021

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