The binding of synthetic retinoids to lipocalin beta-lactoglobulins.
The binding of therapeutically relevant synthetic retinoid derivatives to bovine and reindeer beta-lactoglobulin (betaLG) 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 betaLG homologues with nanomolar K(d) values, and the interaction diminishes the pH-dependent aggregation of retinoids. Thus, betaLG may show benefits in improving the bioavailability of retinoid derivatives.
Riihimäki-Lampén
Laura H
LH
Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), FI-00014 University of Helsinki, Finland.
Vainio
Mikko J
MJ
Vahermo
Mikko
M
Pohjala
Leena L
LL
Heikura
Jonna M S
JM
Valkonen
Kaija H
KH
Virtanen
Vesa T
VT
Yli-Kauhaluoma
Jari T
JT
Vuorela
Pia M
PM
D000818:Animals; D001665:Binding Sites; D001682:Biological Availability; D002417:Cattle; D018360:Crystallography, X-Ray; D015195:Drug Design; D006863:Hydrogen-Ion Concentration; D007782:Lactoglobulins / Q000737:chemistry*; D054834:Lipocalins / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure; D012053:Reindeer; D012176:Retinoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D007782:Lactoglobulins; D054834:Lipocalins; D012176:Retinoids