Abstract

Vitamin D3 is synthesized in the skin from 7-dihydrocholesterol and then hydroxylated to 25-hydroxyvitamin D3 in the liver and, subsequently in the kidney, to the most active hormonal form of vitamin D3, namely, 1?,25-dihydroxy vitamin D3 (1?,25-(OH)2D3, calcitriol). It has been established that 1?,25-(OH)2D3 stimulates intestinal calcium absorption and mobilizes calcium from bone. Recently, an important function of 1?,25-(OH)2D3 in monocytic differentiation of human promyelocytic leukemia cells (HL-60) has been discovered. Recently, 20-hydroxy and alkoxy analogs of 1?,25-(OH)2D3 have been described and are being examined as potential drugs for osteoporosis (e.g. ED-71). We prepared both 2?- and 2?-hydroxy analogs of 19-nor-1?,25-(OH)2D3 and their alkoxy derivatives. These analogs exhibited selective calcemic activity and, moreover, showed high HL-60 differentiation activity. In our continuing investigation of structure-activity relationship of the vitamin D molecule, we have also synthesized 1?- and 2??-alkyl and hydroxyalkyl analogs of 19-nor-1?,25-(OH)2D3. Configurations of the A-ring fragment substituents were determined by 1H, 1H COSY 2D spectra and 1H NOE difference NMR spectroscopy.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Center for Research Resources (NCRR)
Type
Biotechnology Resource Grants (P41)
Project #
5P41RR002301-17
Application #
6451244
Study Section
Project Start
2001-03-01
Project End
2002-02-28
Budget Start
Budget End
Support Year
17
Fiscal Year
2001
Total Cost
Indirect Cost

  Institution

Name
University of Wisconsin Madison
Department
Type
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715

  Publications

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Assadi-Porter, Fariba M; Radek, James; Rao, Hongyu et al. (2018) Multimodal Ligand Binding Studies of Human and Mouse G-Coupled Taste Receptors to Correlate Their Species-Specific Sweetness Tasting Properties. Molecules 23:
Wijayatunga, Nadeeja N; Sams, Valerie G; Dawson, John A et al. (2018) Roux-en-Y gastric bypass surgery alters serum metabolites and fatty acids in patients with morbid obesity. Diabetes Metab Res Rev 34:e3045
Assadi-Porter, Fariba M; Reiland, Hannah; Sabatini, Martina et al. (2018) Metabolic Reprogramming by 3-Iodothyronamine (T1AM): A New Perspective to Reverse Obesity through Co-Regulation of Sirtuin 4 and 6 Expression. Int J Mol Sci 19:
Dominguez, Eddie; Zarnowski, Robert; Sanchez, Hiram et al. (2018) Conservation and Divergence in the Candida Species Biofilm Matrix Mannan-Glucan Complex Structure, Function, and Genetic Control. MBio 9:
Franco, Aldo; Dovell, Sanaz; Möller, Carolina et al. (2018) Structural plasticity of mini-M conotoxins - expression of all mini-M subtypes by Conus regius. FEBS J 285:887-902
Wales, Jessica A; Chen, Cheng-Yu; Breci, Linda et al. (2018) Discovery of stimulator binding to a conserved pocket in the heme domain of soluble guanylyl cyclase. J Biol Chem 293:1850-1864
Selen Alpergin, Ebru S; Bolandnazar, Zeinab; Sabatini, Martina et al. (2017) Metabolic profiling reveals reprogramming of lipid metabolic pathways in treatment of polycystic ovary syndrome with 3-iodothyronamine. Physiol Rep 5:
Mong, Surin K; Cochran, Frank V; Yu, Hongtao et al. (2017) Heterochiral Knottin Protein: Folding and Solution Structure. Biochemistry 56:5720-5725

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