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Chirality2020; 32(3); 334-344; doi: 10.1002/chir.23162

Structural investigations of stereoselective profen binding by equine and leporine serum albumins.

Abstract: Serum albumin, the most abundant transport protein of mammalian blood, interacts with various nonsteroidal anti-inflammatory drugs (NSAIDs) affecting their disposition, metabolism, and excretion. A big group of chiral NSAIDs transported by albumin, profens, is created by derivatives of 2-arylpropionic acid. The chiral center in the structures of profens is adjacent to the carboxylate moiety and often determines different pharmacological properties of profen enantiomers. This study describes crystal structures of two albumins, isolated from equine and leporine serum, in complexes with three profens: ibuprofen, ketoprofen, and suprofen. Based on three-dimensional structures, the stereoselectivity of albumin is discussed and referred to the previously published albumin complexes with drugs. Drug Site 2 (DS2) of albumin, the bulky hydrophobic pocket of subdomain IIIA with a patch of polar residues, preferentially binds (S)-enantiomers of all investigated profens. Almost identical binding mode of all these drugs clearly indicates the stereoselectivity of DS2 towards (S)-profens in different albumin species. Also, the affinity studies show that DS2 is the major site that presents high affinity towards investigated drugs. Additionally, crystallographic data reveal the secondary binding sites of ketoprofen in leporine serum albumin and ibuprofen in equine serum albumin, both overlapping with previously identified naproxen binding sites: the cleft formed between subdomains IIIA and IIIB close to the fatty acid binding site 5 and the niche created between subdomains IIA and IIIA, called fatty acid site 6.
© 2020 Wiley Periodicals, Inc.
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Publication Date: 2020-01-06 PubMed ID: 31905261DOI: 10.1002/chir.23162Google Scholar: Lookup
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  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research studied how the equine and leporine species of albumin, a blood transport protein, interact with different types of nonsteroidal anti-inflammatory drugs known as profens. The study reveals that albumin predominantly binds with the (S)-enantiomers of profens among other findings.

Background of the Study

  • The study seeks to understand the interaction between Serum Albumin, a transport protein present in mammalian blood, and a group of chiral Nonsteroidal Anti-Inflammatory Drugs (NSAIDs), known as profens, (examples being ibuprofen, ketoprofen, and suprofen).
  • Previous research identified that Albumin plays a significant role in influencing the disposition, metabolism, and excretion of various NSAIDs in the body.
  • The profens, being chiral, have a central structure that often determines their pharmacological properties.

Findings of the Study

  • The study describes the crystal structures of albumin isolated from the serum of two different species – horses (equine) and rabbits (leporine), when binding with three types of profen NSAIDs: ibuprofen, ketoprofen, and suprofen.
  • The researchers found that Drug Site 2 (DS2) of albumin, a hydrophobic pocket in the subdomain IIIA, preferentially binds with the (S)-enantiomers of all profens tested in the study.
  • It was noted that the method of binding for all drugs tested was nearly the same, indicating that DS2 has a specific stereoselectivity for the (S)-profens across different albumin species.
  • The study also showed that DS2 presented a higher level of affinity towards the drugs investigated compared to other sites.

Additional Observations

  • Further, the study found secondary binding sites in leporine serum albumin for ketoprofen and in equine serum albumin for ibuprofen. These secondary sites coincide with previously identified binding sites for another common NSAID, naproxen.
  • These secondary sites are located in the cleft between subdomains IIIA and IIIB, close to the fatty acid binding site 5, and the niche created between subdomains IIA and IIIA, known as fatty acid site 6.

Cite This Article

APA
Zielinski K, Sekula B, Bujacz A, Szymczak I. (2020). Structural investigations of stereoselective profen binding by equine and leporine serum albumins. Chirality, 32(3), 334-344. https://doi.org/10.1002/chir.23162

Publication

Chirality
ISSN: 1520-636X
NlmUniqueID: 8914261
Country: United States
Language: English
Volume: 32
Issue: 3
Pages: 334-344

Researcher Affiliations

Zielinski, Kamil
  • Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Lodz, Poland.
Sekula, Bartosz
  • Synchrotron Radiation Research Section of MCL, National Cancer Institute, Argonne, IL, USA.
  • Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Lodz, Poland.
Bujacz, Anna
  • Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Lodz, Poland.
Szymczak, Izabela
  • Institute of Molecular and Industrial Biotechnology, Lodz University of Technology, Lodz, Poland.

MeSH Terms

  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / metabolism
  • Binding Sites
  • Calorimetry
  • Crystallography, X-Ray
  • Hares
  • Horses
  • Ibuprofen / chemistry
  • Ibuprofen / metabolism
  • Ketoprofen / chemistry
  • Ketoprofen / metabolism
  • Models, Molecular
  • Protein Conformation
  • Serum Albumin / chemistry
  • Serum Albumin / metabolism
  • Stereoisomerism
  • Suprofen / chemistry
  • Suprofen / metabolism
  • Thermodynamics

Grant Funding

  • 283570 / BioStruct-X
  • FP7/2007-2013 / European Community
  • 2013/11/B/ST5/02271 / National Science Centre of Poland
  • 2014/12/T/ST5/00136 / National Science Centre of Poland

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Citations

This article has been cited 9 times.
  1. Duszynski K, Sekula B, Talaj J, Bujacz A. Structural Interactions of β-Lactam Antibiotics with Mammalian Serum Albumins. Int J Mol Sci 2026 Jan 13;27(2).
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