Substitution at the C-3 Position of Catechins Has an Influence on the Binding Affinities against Serum Albumin
Masaki Ikeda,
Manabu Ueda-Wakagi,
Kaori Hayashibara,
Rei Kitano,
Masaya Kawase,
Kunihiro Kaihatsu,
Nobuo Kato,
Yoshitomo Suhara,
Naomi Osakabe,
Hitoshi Ashida
Affiliations
Masaki Ikeda
Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan
Manabu Ueda-Wakagi
National Agriculture and Food Research Organization, National Food Research Institute, Tsukuba, Ibaraki 305-8642, Japan
Kaori Hayashibara
Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan
Rei Kitano
Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan
Masaya Kawase
Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura-cho, Nagahama, Shiga 526-0829, Japan
Kunihiro Kaihatsu
Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Nobuo Kato
Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 8-1, Mihogaoka, Ibaraki, Osaka 567-0047, Japan
Yoshitomo Suhara
Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan
Naomi Osakabe
Department of Bioscience and Engineering, College of Systems Engineering and Science, Shibaura Institute of Technology, 307 Fukasaku, Minuma-ku, Saitama 337-8570, Japan
Hitoshi Ashida
Graduate School of Agricultural Science, Kobe University, 1-1 Rokkodai, Nada-ku, Kobe, Hyogo 657-8501, Japan
It is known that catechins interact with the tryptophan (Trp) residue at the drug-binding site of serum albumin. In this study, we used catechin derivatives to investigate which position of the catechin structure strongly influences the binding affinity against bovine serum albumin (BSA) and human serum albumin (HSA). A docking simulation showed that (−)-epigallocatechin gallate (EGCg) interacted with both Trp residues of BSA (one at drug-binding site I and the other on the molecular surface), mainly by π–π stacking. Fluorescence analysis showed that EGCg and substituted EGCg caused a red shift of the peak wavelength of Trp similarly to warfarin (a drug-binding site I-specific compound), while 3-O-acyl-catechins caused a blue shift. To evaluate the binding affinities, the quenching constants were determined by the Stern–Volmer equation. A gallate ester at the C-3 position increased the quenching constants of the catechins. Against BSA, acyl substitution increased the quenching constant proportionally to the carbon chain lengths of the acyl group, whereas methyl substitution decreased the quenching constant. Against HSA, neither acyl nor methyl substitution affected the quenching constant. In conclusion, substitution at the C-3 position of catechins has an important influence on the binding affinity against serum albumin.