合成视黄醇与脂联素β-乳球蛋白的结合。

The binding of synthetic retinoids to lipocalin beta-lactoglobulins.

机构信息

Division of Pharmaceutical Biology, Faculty of Pharmacy, University of Helsinki, P.O. Box 56 (Viikinkaari 5 E), FI-00014 University of Helsinki, Finland.

出版信息

J Med Chem. 2010 Jan 14;53(1):514-8. doi: 10.1021/jm901309r.

DOI:10.1021/jm901309r

PMID:19938842

Abstract

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.

摘要

采用荧光猝灭法和超滤/高效液相色谱法，研究了治疗相关的合成视黄醇衍生物与牛和驯鹿β-乳球蛋白（βLG）的结合。此外，还描述了甲基（E）-3-[4-[(E)-2-（2,6,6-三甲基环己-1-烯基）乙烯基]苯基]-丙烯酸酯 4 和（E）-3-[4-[(E)-2-（2,6,6-三甲基环己-1-烯基）乙烯基]苯基]丙烯酸 5 的合成。所有研究的化合物均以纳摩尔 K（d）值与两种βLG 同系物结合，这种相互作用降低了视黄醇衍生物的 pH 依赖性聚集。因此，βLG 可能在提高视黄醇衍生物的生物利用度方面显示出益处。