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Amino Acids

, Volume 38, Issue 4, pp 1011–1020 | Cite as

Interactions of α1–proteinase inhibitor with small ligands of therapeutic potential: binding with retinoic acid

  • Elena Karnaukhova
Original Article

Abstract

Human α1–proteinase inhibitor (α1–PI), also known as α1-antitrypsin, is the most abundant plasma serine protease inhibitor (serpin). It is best recognized for inhibition of neutrophil elastase. The α1–PI interactions with non-protease ligands were investigated mainly in regards to those molecules that may block the aggregation of α1–PI Z mutant. The objective of this study was to evaluate the potential of α1–PI to bind small non-peptide ligands of pharmaceutical interest that may attain additional properties to currently available α1–PI therapeutic preparations. Among putative ligands of bio-medical interest examined in this study, all-trans retinoic acid (RA) was selected due to its recently proposed roles in the lungs, and as an efficient optical probe. The results of this study, including absorption spectroscopy data, fluorescence quenching and the protein-induced chirality of the visible circular dichroism strongly suggest that α1–PI does bind RA in vitro to non-covalent complexes of up to two moles of RA per one mole of the protein. To our knowledge, this is the first report that provides experimental evidence of the α1–PI potential towards bi-functional drugs via a combination with RA, or potentially other molecules of pharmaceutical interest, that ultimately, may enhance currently available α1–PI therapies.

Keywords

Alpha-1 proteinase inhibitor Antitrypsin Retinoic acid 

Notes

Acknowledgments

The author is grateful to Drs. Abdu Alayash, Wayne Hicks and Dominador Manalo for helpful discussions and critical reading of the manuscript.

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Copyright information

© Springer-Verlag 2009

Authors and Affiliations

  1. 1.Laboratory of Biochemistry and Vascular Biology, Division of Hematology, Center for Biologics Evaluation and ResearchFood and Drug AdministrationBethesdaUSA

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