Journal of Medicinal Chemistry
ARTICLE
(4) Cowan, S.; Newcomer, M.; Jones, T. Crystallographic refine-
ment of human serum retinol binding protein at 2 Å resolution. Proteins
1990, 8, 44–61.
(24) Redondo, C.; Burke, B.; Findlay, J. The retinol-binding protein
system: A potential paradigm for steroid-binding globulins? Horm.
Metab. Res. 2006, 38, 269–278.
(5) Monaco, H.; Rizzi, M.; Coda, A. Structure of a complex of two
plasma proteins: Transthyretin and retinol-binding protein. Science
1995, 268, 1039–1041.
(25) Sivaprasadarao, A.; Findlay, J. The interaction of retinol-bind-
ing protein with its plasma-membrane receptor. Biochem. J. 1988,
255, 561–569.
(6) Goodman, D. Overview of current knowledge of metabolism of
vitamin A and carotenoids. J. Natl. Cancer Inst. 1984, 73, 1375–1379.
(7) Kawaguchi, R.; Yu, J.; Honda, J.; Hu, J.; Whitelegge, J.; Ping, P.;
Wiita, P.; Bok, D.; Sun, H. A membrane receptor for retinol binding
protein mediates cellular uptake of vitamin A. Science 2007, 315,
820–825.
(8) Kawaguchi, R.; Yu, J.; Wiita, P.; Honda, J.; Sun, H. An essential
ligand-binding domain in the membrane receptor for retinol-binding
protein revealed by large-scale mutagenesis and a human polymorphism.
J. Biol. Chem. 2008, 283, 15160–15168.
(9) Redondo, C.; Vouropoulou, M.; Evans, J.; Findlay, J. Identifica-
tion of the retinol-binding protein (RBP) interaction site and functional
state of RBPs for the membrane receptor. FASEB J. 2008, 22,
1043–1054.
(10) Sivaprasadarao, A.; Sundaram, M.; Findlay, J. Interactions of
retinol-binding protein with transthyretin and its receptor. Methods Mol.
Biol. 1998, 89, 155–163.
(26) Cho, Y.; Youn, B.; Lee, H.; Lee, N.; Min, S.; Kwak, S.; Lee, H.;
Park, K. Plasma retinol-binding protein-4 concentrations are elevated in
human subjects with impaired glucose tolerance and type 2 diabetes.
Diabetes Care 2006, 29, 2457–2461.
(27) Craig, R.; Chu, W.; Elbein, S. Retinol binding protein 4 as a
candidate gene for type 2 diabetes and prediabetic intermediate traits.
Mol. Genet. Metab. 2007, 90, 338–344.
(28) Gavi, S.; Stuart, L.; Kelly, P.; Melendez, M.; Mynarcik, D.;
Gelato, M.; McNurlan, M. Retinol-binding protein 4 is associated with
insulin resistance and body fat distribution in nonobese subjects without
type 2 diabetes. J. Clin. Endocrinol. Metab. 2007, 92, 1886–1890.
(29) Graham, T.; Wason, C.; Bl€uher, M.; Kahn, B. Shortcomings in
methodology complicate measurements of serum retinol binding pro-
tein (RBP4) in insulin-resistant human subjects. Diabetologia 2007,
50, 814–823.
(30) Lee, D.; Lee, J.; Im, J. Association of serum retinol binding
protein 4 and insulin resistance in apparently healthy adolescents.
Metabolism 2007, 56, 327–231.
(31) Janke, J.; Engeli, S.; Boschmann, M.; Adams, F.; B€ohnke, J.;
Luft, F.; Sharma, A.; Jordan, J. Retinol-binding protein 4 in human
obesity. Diabetes 2006, 55, 2805–2810.
(11) Yang, Q.; Graham, T.; Mody, N.; Preitner, F.; Peroni, O.;
Zabolotny, J.; Kotani, K.; Quadro, L.; Kahn, B. Serum retinol binding
protein 4 contributes to insulin resistance in obesity and type 2 diabetes.
Nature 2005, 436, 356–362.
(12) Graham, T.; Yang, Q.; Bl€uher, M.; Hammarstedt, A.; Ciaraldi,
T.; Henry, R.; Wason, C.; Oberbach, A.; Jansson, P.; Smith, U.; Kahn, B.
Retinol-binding protein 4 and insulin resistance in lean, obese, and
diabetic subjects. N. Engl. J. Med. 2006, 354, 2552–2563.
(13) Ost, A.; Danielsson, A.; Lidꢀen, M.; Eriksson, U.; Nystrom, F.;
Stralfors, P. Retinol-binding protein-4 attenuates insulin-induced phos-
phorylation of IRS1 and ERK1/2 in primary human adipocytes. FASEB
J. 2007, 21, 3696–3704.
(14) Zanardi, S.; Serrano, D.; Argusti, A.; Barile, M.; Puntoni, M.;
Decensi, A. Clinical trials with retinoids for breast cancer chemopreven-
tion. Endocr. Relat. Cancer 2006, 13, 51–68.
(15) Radu, R.; Han, Y.; Bui, T.; Nusinowitz, S.; Bok, D.; Lichter, J.;
Widder, K.; Travis, G.; Mata, N. Reductions in serum vitamin A arrest
accumulation of toxic retinal fluorophores: A potential therapy for
treatment of lipofuscin-based retinal diseases. Invest. Ophthalmol. Visual
Sci. 2005, 46, 4393–4401.
(16) Zanotti, G.; Marcello, M.; Malpeli, G.; Folli, C.; Sartori, G.;
Berni, R. Crystallographic studies on complexes between retinoids and
plasma retinol-binding protein. J. Biol. Chem. 1994, 269, 29613–29620.
(17) Berni, R.; Formelli, F. In vitro interaction of fenretinide with
plasma retinol-binding protein and its functional consequences. FEBS
Lett. 1992, 308, 43–45.
(18) Preitner, F.; Mody, N.; Graham, T.; Peroni, O.; Kahn, B. Long-
term Fenretinide treatment prevents high-fat diet-induced obesity,
insulin resistance, and hepatic steatosis. Am. J. Physiol. 2009,
297, E1420–E1429.
(32) Takashima, N.; Tomoike, H.; Iwai, N. Retinol-binding protein
4 and insulin resistance. N. Engl. J. Med. 2006, 355, 1392, author reply
1394ꢀ1395.
(33) Manolescu, D.; Sima, A.; Bhat, P. All-trans retinoic acid lowers
serum retinol-binding protein 4 concentrations and increases insulin
sensitivity in diabetic mice. J. Nutr. 2010, 140, 311–316.
(34) Noy, N.; Xu, Z. Interactions of retinol with binding proteins:
Implications for the mechanism of uptake by cells. Biochemistry 1990,
29, 3878–3883.
ꢂ
(35) Berni, R.; Clerici, M.; Malpeli, G.; Cleris, L.; Formelli, F.
Retinoids: In vitro interaction with retinol-binding protein and influence
on plasma retinol. FASEB J. 1993, 7, 1179–1184.
(36) Johansson, H.; Gandini, S.; Guerrieri-Gonzaga, A.; Iodice, S.;
Ruscica, M.; Bonanni, B.; Gulisano, M.; Magni, P.; Formelli, F.; Decensi,
A. Effect of fenretinide and low-dose tamoxifen on insulin sensitivity in
premenopausal women at high risk for breast cancer. Cancer Res. 2008,
68, 9512–9518.
(37) Xie, Y.; Lashuel, H.; Miroy, G.; Dikler, S.; Kelly, J. Recombinant
human retinol-binding protein refolding, native disulfide formation, and
characterization. Protein Expression Purif. 1998, 14, 31–37.
(38) Lashuel, H.; Wurth, C.; Woo, L.; Kelly, J. The most pathogenic
transthyretin variant, L55P, forms amyloid fibrils under acidic conditions
and protofilaments under physiological conditions. Biochemistry 1999,
38, 13560–13573.
(39) DeLano, W. L. (2002) The PyMOL Molecular Graphics System,
DeLano Scientific, Palo Alto, CA.
(19) Cogan, U.; Kopelman, M.; Mokady, S.; Shinitzky, M. Binding
affinities of retinol and related compounds to retinol binding proteins.
Eur. J. Biochem. 1976, 65, 71–78.
(20) MOE (2008) Chemical Computing Group.
(21) Malpeli, G.; Folli, C.; Berni, R. Retinoid binding to retinol-
binding protein and the interference with the interaction with transthyr-
etin. Biochim. Biophys. Acta 1996, 1294, 48–54.
(22) Coward, P.; Conn, M.; Tang, J.; Xiong, F.; Menjares, A.;
Reagan, J. Application of an allosteric model to describe the interactions
among retinol binding protein 4, transthyretin, and small molecule
retinol binding protein 4 ligands. Anal. Biochem. 2009, 384, 312–320.
(23) Wysocka-Kapcinska, M.; Campos-Sandoval, J.; Pal, A.; Findlay,
J. Expression and characterization of recombinant human retinol-
binding protein in Pichia pastoris. Protein Expression Purif. 2010, 71,
28–32.
4387
dx.doi.org/10.1021/jm200256g |J. Med. Chem. 2011, 54, 4378–4387