TOP
OF PAGEA. Syntheses and applications of novel analogs of cholesterol, glycerolipids, and sphingolipids
B. New methodology for the preparation of natural and unnatural sphingolipids
D. Synthesis and properties of unnatural ceramides with anticancer activity in vitro
E. Labeled cerebrosides: synthesis and applications in membrane research
F. Ether-linked glycerolipids with anticancer activity in vitro
G. Calorimetric studies of phospholipids
We make synthetic sphingolipid analogs available for collaborations with NHLBI-funded investigators and other professional researchers in the scientific community whose studies are pertinent to cardiovascular and lung biology and sphingolipid-mediated signaling events. Requests for compounds should be submitted to robert.bittman@qc.cuny.edu
A. Publications related to the syntheses and applications of novel analogs of cholesterol, glycerolipids, and sphingolipids to provide insights about biological or biophysical problems
Cholesterol:
N. Zhong, H.-S. Byun, and R. Bittman, "Hydrophilic Cholesterol-binding Molecular Imprinted Polymers," Tetrahedron Lett. 42, 1839-1841 (2001).
N. Zhong, H. Ohvo-Rekilä, B. Ramstedt, J. P. Slotte, and R. Bittman, "Removal of Cholesterol and Palmitic Acid from Langmuir Monolayers by Complexation with New Water-soluble Cyclodextrin Derivatives," Langmuir 17, 5319-5323 (2001).
X. Xu, R. Bittman, C. Vilchèze, G. Duportail, and E. London, "Effect of the Structure of Natural Sterols and Sphingolipids on the Formation of Ordered Sphingolipid/Sterol Domains (Rafts): Comparison of Cholesterol to Plant, Fungal, and Disease-Associated Sterols, and Comparison of Sphingomyelin, Cerebrosides, and Ceramide," J. Biol. Chem. 276, 33540-33546 (2001).
J. R. Harris, S. Bhakdi, U. Meissner, D. Scheffler, R. Bittman, G. Li, A. Zitzer, and M. Palmer, "Interaction of the Vibrio cholerae Cytolysin (VCC) with Cholesterol, Some Cholesterol Esters, and Cholesterol Derivatives: A TEM Study," J. Struct. Biol. 139, 122-135 (2002).
M. Merris, W. G. Wadsworth, U. Khamrai, R. Bittman, D. J. Chitwood, and J. Lenard, "Sterol Effects and Sites of Sterol Accumulation in Caenorhabditis elegans: Developmental Requirement for 4a-Methylsterol," J. Lipid Res. 44, 172-181 (2003).
Z. Li, E. Mintzer, and R. Bittman, “First Synthesis of Free Cholesterol – BODIPY Conjugates,” J. Org. Chem. 71, 1718-1721 (2006).
J. E. Shaw, R. F. Epand, R. M. Epand, Z. Li, R. Bittman, and C. M. Yip, “Correlated Fluorescence-AFM Microscopy of Membrane Domains: Structure of Fluorescence Probes Determines Lipid Localization,” Biophys. J. 90, 2170-2178 (2006).
Sphingomyelin:
B.-L. Waarts, R. Bittman, and J. Wilschut, "Sphingolipid- and Cholesterol-Dependence of Alphavirus Membrane Fusion. Lack of Correlation with Lipid Raft Formation in Target Liposomes," J. Biol. Chem. 277, 38141-38147 (2002).
T. Mehnert, R. Bittman, R. Jacob, and K. Beyer, “Structure and Lipid Interaction of N-Palmitoylsphingomyelin in Bilayer Membranes as Revealed by 2H NMR Spectroscopy,” Biophys. J. 90, 939-946 (2006).
Glycerolipids:
R. Bittman, D. Qin, D.-A. Wang, G. Tigyi, P. Samadder, and G. Arthur, "Synthesis and Anti-tumor Properties of a Plasmalogen Methyl Ether Analogue," Tetrahedron 57, 4277-4282 (2001).
G. Li, P. Samadder, G. Arthur, and R. Bittman, "Synthesis and Antiproliferative Properties of a Photoactivatable Analogue of ET-18-OCH3," Tetrahedron 57, 8925-8932 (2001).
K. Yokoyama, D. L. Baker, T. Virag, K. Liliom, H.-S. Byun, G. Tigyi, G., and R. Bittman, "Stereochemical Properties of Lysophosphatidic Acid Receptor Activation and Metabolism," Biochim. Biophys. Acta 1582, 295-308 (2002).
C. Zhang, D. L. Baker, S. Yasuda, N. Makarova, L. Johnson, L. Balazs, G. Marathe, T. M. McIntyre, Y. Xu, G. D. Prestwich, H.-S. Byun, R. Bittman, and G. Tigyi, "Lysophosphatidic Acid Induces Neointima Formation Through PPARg Activation," J. Exp. Med. 199, 763-774 (2004).
T. Tsukahara,R. Tsukahara, S. Yasuda, N. Makarova, W. J. Valentine, P. Allison, H. Yuan, D. L. Baker, Z. Li, R. Bittman, A. Parrill, and G. Tigyi, “Different Residues Mediate Recognition of 1-O-Oleyl-lysophosphatidic Acid and Rosiglitazone in the Ligand-Binding Domain of Peroxisone Proliferator-activated Receptor g,” J. Biol. Chem. 281, 3398-3407 (2006).
Ceramides:
A. Zitzer, R. Bittman, C. A. Verbicky, R. K. Erukulla, S. Bhakdi, S. Weis, A. Valeva, and M. Palmer, "Coupling of Cholesterol and Cone-shaped Lipids in Bilayers Augments Membrane Permeabilization by the Cholesterol-specific Toxins Streptolysin O and Vibrio cholerae Cytolysin," J. Biol. Chem. 276, 14628-14633 (2001).
H. L. Brockman, M. M. Momsen, R. E. Brown, L. He, J. Chun, H.-S. Byun, and R. Bittman, "The 4,5-Double Bond of Ceramide Regulates Its Dipole Potential, Elastic Properties, and Packing Behavior," Biophys. J. 87, 1722-1731 (2004).
B. Publications related to new methodology for the preparation of natural and unnatural sphingolipids
L. He, H.-S. Byun, and R. Bittman, "A Stereocontrolled, Efficient Synthetic Route to Bioactive Sphingolipids: Synthesis of Phytosphingosine and Phytoceramides from Unsaturated Ester Precursors via Cyclic Sulfate Intermediates," J. Org. Chem. 65, 7618-7626 (2000).
L. He, H.-S. Byun, and R. Bittman, "Stereoselective Preparation of Ceramide and Its Skeleton Backbone Modified Analogues via Cyclic Thionocarbonate Intermediates Derived by Catalytic Asymmetric Dihydroxylation of a,b-Unsaturated Ester Precursors," J. Org. Chem. 65, 7627-7633 (2000).
J. Chun, L. He, H.-S. Byun, and R. Bittman, "Synthesis of Ceramide Analogues Having the C(4)-C(5) Bond of the Long-chain Base as Part of an Aromatic or Heteroaromatic System, J. Org. Chem. 65, 7634-7640 (2000).
R. Bittman and C. A. Verbicky, "Methanolysis of Sphingomyelin: Toward an Epimerization-free Methodology for the Preparation of D-erythro-sphingosylphosphoryl-choline," J. Lipid Res. 41, 2089-2093 (2000).
J. Chun, G. Li, H.-S. Byun, and R. Bittman, "A Concise Route to D-erythro-Sphingosine from N-Boc-L-serine Derivatives via Sulfoxide or Sulfone Intermediates," Tetrahedron Lett. 43, 375-377 (2002).
J. Chun, G. Li, H.-S. Byun, and R. Bittman, "Synthesis of New Trans Double Bond Sphingolipid Analogues: D4,6 and D6 Ceramides," J. Org. Chem. 67, 2600-2605 (2002).
J. Chun, H.-S. Byun, and R. Bittman, "First Asymmetric Synthesis of 6-Hydroxy-4-Sphingenine-containing Ceramides. Use of Chiral Propargylic Alcohols to Prepare a Lipid Found in Human Skin," J. Org. Chem. 68, 348-354 (2003).
X. Lu, H.-S. Byun, and R. Bittman, "Synthesis of L-lyxo-Phytosphingosine and Its 1-Phosphonate Analogue Using a Threitol Acetal Synthon," J. Org. Chem. 69, 5433-5438 (2004).
C. Sun and R. Bittman, "An Efficient Preparation of Isosteric Phosphonate Analogues of Sphingolipids by Opening of Oxirane and Cyclic Sulfamidate Intermediates with a-Lithiated Alkylphosphonic Esters," J. Org. Chem. 69, 7694-7699 (2004).
X. Lu and R. Bittman, "Efficient and Versatile Synthesis of (2S,3R)-Sphingosine and Its 2-Azido-3-O-benzoyl Analogue," Tetrahedron Lett. 46, 1873-1875 (2005).
X. Lu and R. Bittman, “Enantioselective Synthesis of the Phosphate Esters of the Immunosuppressive Lipid FTY720,” Tetrahedron Lett. 47, 825-827 (2006).
H.-S. Byun, X. Lu, and R. Bittman, “Stereoselective Total Synthesis of Serine Palmitoyl-CoA Transferase Inhibitors,” Synthesis, in press (2006).
C. Publications related to photoreactive lipids
G. Li and R. Bittman, "Synthesis of Novel Phenoxy-linked Diazirine Glycero- and Sphingolipid Probes via Trialkylaryltin Intermediates," Tetrahedron Lett. 41, 6737-6741 (2000).
G. Li, P. Samadder, G. Arthur, and R. Bittman, "Synthesis and Antiproliferative Properties of a Photoactivatable Analogue of ET-18-OCH3," Tetrahedron 57, 8925-8932 (2001).
E. A. Mintzer, B.-L. Waarts, J. Wilschut, and R. Bittman, "Behavior of a Photoactivatable Analog of Cholesterol, 6-Photocholesterol, in Model Membranes," FEBS Lett. 501, 181-184 (2002).
X. Lu, S. Cseh, H.-S. Byun, G. Tigyi, and R. Bittman, "Total Synthesis of Two Photoactivatable Analogues of the Growth Factor-like Mediator Sphingosine 1-Phosphate: Differential Interaction with Protein Targets," J. Org. Chem. 68, 7046-7050 (2003).
X. Lu and R. Bittman, “Synthesis of a Photoactivatable (2S,3R)-Sphingosylphosphorylcholine Analogue,” J. Org. Chem. 70, 4746-4750 (2005).
Z. Li, D. L. Baker, G. Tigyi, and R. Bittman, “Synthesis of Photoactivatable Analogues of Lysophosphatidic Acid and Covalent Labeling of Plasma Proteins,” J. Org. Chem. 71, 629-635 (2006).
C. Sun and R. Bittman, “A Photoreactive Analogue of the Immunosuppressant FTY720,” J. Org. Chem. 71, 2200-2202 (2006).
D. Publications related to the synthesis and properties of unnatural ceramides with anticancer activity in vitro
J. Chun, H.-S. Byun, G. Arthur, and R. Bittman, "Synthesis and Growth Inhibitory Activity of Chiral 5-Hydroxy-2-N-acyl-3E-sphingenines: Ceramides with an Unusual Sphingoid Backbone," J. Org. Chem. 68, 355-359 (2003).
K. W. Crawford, R. Bittman, J. Chun, H.-S. Byun, and W. D. Bowen, “Novel Ceramide Analogues Display Selective Cytotoxicity in Drug-resistant Breast Tumor Cell Lines Compared to Normal Breast Epithelial Cells,” Cell. Mol. Biol. 49, 1017-1023 (2003).
A. P. Struckhoff, R. Bittman, M. E. Burow, S. Clejan, S. Eliot, T. Hammond, A. B. Scandurro, Y. Tang, and B. S. Beckman, "Novel Ceramide Analogs as Potential Chemotherapeutic Agents in Breast Cancer," J. Pharmacol. Exp. Ther. 309, 523-532 (2004).X. Lu, G. Arthur, and R. Bittman, “Synthesis of a Novel Ceramide Analogue via Tebbe Methylenation and Evaluation of Its Antiproliferative Activity,” Org. Lett. 7, 1645-1648 (2005).
E. Publications related to labeled cerebrosides: synthesis and applications in membrane research
P. Mattjus, B. Malewicz, J. T. Valiyaveettil, W. J. Baumann, R. Bittman, and R. E. Brown, "Sphingomyelin Modulates the Transbilayer Distribution of Galactosylceramide in Phospholipid Membranes," J. Biol. Chem. 277, 19476-19481 (2002).
R. D. Singh, V. Puri, J. T. Valiyaveettil, D. L. Marks, R. Bittman, and R. E. Pagano, "Selective Caveolin-1-dependent Endocytosis of Glycosphingolipids," Mol. Biol. Cell 14, 3254-3265 (2003).
B. Malewicz, J. T. Valiyaveettil, K. Jacob, H.-S. Byun, P. Mattjus, W. J. Baumann, R. Bittman, and R. E. Brown, "The 3-Hydroxy Group and 4,5-trans Double Bond of Sphingomyelin Are Essential for Modulation of Galactosylceramide Transmembrane Asymmetry," Biophys. J. 88, 2670-2680 (2005).
Y. Liu and R. Bittman, “Synthesis of Fluorescent Lactosylceramide Stereoisomers,” Chem. Phys. Lipids, in press (2006).
F. Publications related to ether-linked glycerolipids with anticancer activity in vitro
G. Yang, R. W. Franck, R. Bittman, P. Samadder, and G. Arthur, "Synthesis and Growth-Inhibitory Properties of Glucosamine-derived Glycerolipids," Org. Letters 3, 197-200 (2001).
R. Bittman, W. R. Perkins, and C. E. Swenson, "TLC ELL-12: Liposomal ET-18-OCH3," Drugs Fut. 26, 1052-1058 (2001).
P. Samadder, C. Richards, R. Bittman, , R. P. Bhullar, and G. Arthur, “The Antitumor Ether Lipid 1-O-Octadecyl-2-O-methyl-rac-glycerophosphocholine (ET-18-OCH3) Inhibits the Association between Ras and Raf-1,” Anticancer Res. 23, 2291-2296 (2003).
P. Samadder, R. Bittman, H.-S. Byun, R. Bhullar, and G. Arthur, "The Differential Modulation of Signaling Pathways and Epithelial Cancer Cell Proliferation by the S and R Enantiomers of 2’-(Trimethylammonio)ethyl 4-(Hexadecyloxy)-3-methoxy-1-butene-phosphonate, Novel Phospholipid Antitumor Agents," J. Med. Chem. 47, 2710-2713 (2004).
G. Arthur, P. Samadder, and R. Bittman, "ET-18-OCH3 Inhibits the Phosphorylation and Activation of p70 S6 Kinase in MCF-7 Cells," Anticancer Res. 24, 95-100 (2005).
G. Publications related to calorimetric studies of phospholipids
Z. Li, E. Mintzer, and R. Bittman, "The Critical Micelle Concentrations of Lyso-phosphatidic Acid and Sphingosylphosphorylcholine," Chem. Phys. Lipids 130, 197-201 (2004).
E. Mintzer, H. Sargsyan, and R. Bittman, “Lysophosphatidic Acid and Lipopolysaccharide Bind to the PIP2-Binding Domain of Gelsolin,” Biochim. Biophys. Acta 1758, 85-89 (2006).
Last updated April 21, 2006.