The Binding of Synthetic Retinoids to Lipocalin β-Lactoglobulins

• Published in: Journal of medicinal chemistry Vol. 53; no. 1; pp. 514 - 518
• Main Authors: Riihimäki-Lampén, Laura H, Vainio, Mikko J, Vahermo, Mikko, Pohjala, Leena L, Heikura, Jonna M. S, Valkonen, Kaija H, Virtanen, Vesa T, Yli-Kauhaluoma, Jari T, Vuorela, Pia M
• Format: Journal Article
• Language: English
• Published: Columbus, OH American Chemical Society 14-01-2010
• Subjects: Animals; Binding Sites; Biological and medical sciences; Biological Availability; Cattle; Crystallography, X-Ray; Drug Design; Hydrogen-Ion Concentration; Lactoglobulins - chemistry; Lipocalins - chemistry; Medical sciences; Miscellaneous; Models, Molecular; Molecular Structure; Pharmacology. Drug treatments; Reindeer; Retinoids - chemical synthesis; Retinoids - chemistry; Retinoids - pharmacology; Structure-Activity Relationship; Retinoid; Fluorescence; Molecular interaction; Aggregation; Ester; Ultrafiltration; Carboxylic acid; Trans stereoisomer; Chemical synthesis; Ungulata; Carrier protein; Bovine; β-Lactoglobulin; Lipocalin; Glycoprotein; Stability constant; Bioavailability; In vitro; Biological activity; Protein; Vertebrata; Biological fixation; Mammalia; Animal; Phenols; Carboxamide; Reindeer; Artiodactyla; Pharmacokinetics
• ISSN: 0022-2623; 1520-4804
• DOI: 10.1021/jm901309r

The binding of therapeutically relevant synthetic retinoid derivatives to bovine and reindeer β-lactoglobulin (βLG) is demonstrated using fluorescence quenching and ultrafiltration/HPLC methods. Furthermore, synthesis of methyl (E)-3-[4-[(E)-2-(2,6,6-trimethylcyclohex-1-enyl)vinyl]phenyl]-acrylate 4 and (E)-3-[4-[(E)-2-(2,6,6-trimethylcyclohex-1-enyl)vinyl]phenyl]acrylic acid 5 is described. All studied compounds bind to both βLG homologues with nanomolar K d values, and the interaction diminishes the pH-dependent aggregation of retinoids. Thus, βLG may show benefits in improving the bioavailability of retinoid derivatives.