Carbohydrate-based bioactive compounds for medicinal chemistry applications

Mini-Reviews in Medicinal Chemistry

Volumn 11, Issue 1, 2011, Pages 39-54

  Cipolla, L ^a   Peri, F ^a  

^a UNIVERSITY OF MILANO BICOCCA   (Italy)

Author keywords

Carbohydrates; Glycidic scaffolds; Glycobiology; Glycochemistry; Glycoconjugates; Glycomimetics; Medicinal chemistry; Peptidomimetics

Indexed keywords

CARBOHYDRATE DERIVATIVE; FUNCTIONAL GROUP; GLYCAN DERIVATIVE; GLYCOCONJUGATE; GLYCOLIPID; GLYCOPEPTIDE; HYDROXYL GROUP; LIGAND; MONOSACCHARIDE; OLIGOSACCHARIDE;

ARTICLE; BIOMIMETICS; CHEMICAL GENETICS; COMPLEX FORMATION; DRUG MECHANISM; DRUG RECEPTOR BINDING; DRUG SYNTHESIS; GLYCOSYLATION; MOLECULAR PROBE; NONHUMAN; PHARMACOPHORE; STEREOCHEMISTRY; STRUCTURE ACTIVITY RELATION;

ANIMALS; BIOMIMETIC MATERIALS; CARBOHYDRATES; CHEMISTRY, PHARMACEUTICAL; HUMANS;

EID: 78650913469     PISSN: 13895575     EISSN: None     Source Type: Journal    
DOI: 10.2174/138955711793564060     Document Type: Article

References (96)

1. Gabius, H.-J The Sugar Code: Fundamentals Of Glycosciences, Wiley, 2009
2. Lowe, J.B.; Marth, J.D. A genetic approach to mammalian glycan function. Annu. Rev. Biochem., 2003, 72, 643-691.
3. Freeze, H.H. Genetic defects in the human glycome. Nat. Rev. Genet., 2006, 7, 537-51.
4. Rudd, P.M.; Wormald, M.R.; Dwek, R.A. Sugar-mediated ligand-receptor interactions in the immune system Trends Biotechnol., 2004, 22, 524-530.
5. Dwek, R.A.; Butters, T.D.; Platt, F.M.; Zitzmann, N. Targeting glycosylation as a therapeutic approach. Nat. Rev. Drug Discov., 2002, 1, 65-75.
6. Wong CH. Carbohydrate-based Drug Discovery. Wiley-VCH Weinheim, 2003.
7. Babu, Y.; Sudhakara; C.; Pooran; K.; Pravin, L. Influenza neu raminidase inhibitors as antiviral agents. Ann. Rep. Med. Chem., 2006, 41, 287-97;
8. Democratis, J.; Pareek, M.; Stephenson, I. Use of neuraminidase inhibitors to combat pandemic influenza. J. Antimicrob. Chemother., 2006, 58, 911-5.
9. De Clercq, E. Antiviral agents active against influenza A viruses. Nat. Rev. Drug Discov., 2006, 5, 1015-1025.
10. Gruters, R.A.; Neefjes, J.J.; Tersmette, M.; De Goede, R.E.; Tulp, A.; Huisman, H.G.; Miedema, F.; Ploegh, H.L. Interference with HIV-induced syncytium formation and viral infectivity by inhibitors of trimming glucosidase. Nature, 1987, 330, 74-77.
11. Cipolla, L.; La Ferla, B.; Gregori, M. Combinatorial approaches to iminosugars as glycosidase and glycosyltransferase inhibitors. Comb. Chem. High Throughput Screen. 2006, 9, 571-582.
12. Ernst, B.; Magnani, J.L. From carbohydrate leads to glycomimetic drugs. Nat. Rev. Drug Discov., 2009, 8, 661-677.
13. Gravier-Pelletier, C.; Le Merrer, Y. Synthesis of Scaffolds with Glycomimetic Structures. Curr. Org. Synth. 2007, 4, 1-13.
14. Murphy, P.V. Peptidomimetics, Glycomimetics and Scaffolds from Carbohydrate Building Blocks. Eur. J. Org. Chem., 2007, 4177-4187.
15. Ohtsubo, K.; Marth, J.D. Glycosylation in Cellular Mechanisms of Health and Disease. Cell, 2006, 126, 855-867.
16. Asano, N.; Nash, R.J.; Molyneux, R.J.; Fleet, G.W.J. Sugar-mimic glycosidase inhibitors: natural occurrence, biological activity and prospects for therapeutic application. Tetrahedron: Asymm., 2000, 11, 1645-1680.
17. Lillelund, V.H.; Jensen, H.H.; Liang, X.; Bols, M. Recent developments of transition-state analogue glycosidase inhibitors of non-natural product origin. Chem. Rev., 2002, 102, 515-533.
18. Inouye, S.; Tsuruoka, T.; Niida, T. The structure of nojirimycin, a piperidinose sugar antibiotic. J. Antibiot., 1966, 19, 288-292.
19. Liu, P.S. Total synthesis of 2,6-dideoxy-2,6-imino-7-O-(-D- glucopyranosyl)-D-glycero-L-gulo-heptitol hydrochloride. A potent inhibitor of -glucosidases J. Org. Chem., 1987, 52, 4717-4721.
20. Kite, G.C.; Fellows, L.E.; Fleet, G.W.J.; Liu, P.S.; Scofield, A.M.; Smith, N.G. -Homonojirimycin [2,6-dideoxy-2,6-imino-D- glycero-L-gulo-heptitol] from omphalea diandra L.: isolation and glucosidase inhibtion. Tetrahedron Lett., 1988, 29, 6483-6486.
21. Cipolla, L.; La Ferla, B.; Peri, F.; Nicotra, F. A new procedure for the synthesis of C-glycosides of nojirimycin. Chem. Commun., 2000, 1289-1290.
22. Cipolla, L.; Reis Fernandes, M.; Gregori, M.; Airoldi, C.; Nicotra, F. Synthesis and biological evaluation of a small library of nojirimycin derived bicyclic iminosugars. Carbohydr. Res., 2007, 342, 1813-1830.
23. Cohen, J.; Glauser, M. P. Septic shock: treatment. Lancet, 1991, 338, 736-739.
24. Beutler, B TLR4: central component of the sole mammalian LPS sensor. Curr. Opin. Immunol., 2000, 12, 20-6.
25. Beutler, B.; Poltorak, A. Positional cloning of Lps, and the general role of tolllike receptors in the innate immune response. Eur. Ccytokine Netw., 2000, 11, 143-152.
26. Hawkins, L.D.; Christ, W.J.; Rossignol, D.P. Inhibition of endotoxin response by synthetic TLR4 antagonists. Curr. Top. Med. Chem., 2004, 4, 1147-1171;
27. Christ, W.J.; Hawkins, L.D.; Lewis, M.D.; Kishi, Y. Synthetic lipid A antagonists for sepsis treatment. Carbohydr. Based Drug Discov. 2003, 1, 341-355;
28. Martin, O.; Zhou, W.; Wu, X.; Front-Deschamps, S.; Moutel, S.; Schindl, K.; Jeandet, P.; Zbaeren, C.; Bauer, J.A. Synthesis and Immunobiological Activity of an original Series of Acyclic Lipid A Mimics Based on a Pseudodipeptide Backbone. J. Med. Chem., 2006, 49, 6000-6014.
29. Christ, W.J.; Asano, O.; Robidoux, A.L.; Perez, M.; Wang, Y.; Dubuc, G.R.; Gavin, W.E.; Hawkins, L.D.; McGuinness, P.D. Mullarkey, M.A. E5531, a pure endotoxin antagonist of high potency Science, 1995, 268, 80-83.
30. Gutsmann, T.; Schromm, A. B.; Brandenburg, K. The physico-chemistry of endotoxins in relation to bioactivity. Int. J. Med. Mi crobiol., 2007, 297, 341-352.
31. Peri, F.; Granucci, F.; Costa, B.; Zanoni, I.; Marinzi, C.; Nicotra, F. Inhibition of Lipid A Stimulated Activation of Human Dendritic Cells and Macrophages by Amino and Hydroxylamino Monosaccharides. Angew. Chem. Int. Ed. Engl., 2007, 46, 3308-3312.
32. Piazza, M.; Rossini, C.; Della Fiorentina, S.; Pozzi, C.; Comelli, F.; Bettoni, I.; Fusi, P.; Costa, B.; Peri, F.Glycolipids and benzylam-characterization J. Med. Chem., 2009, 52, 1209-1213.
33. Peri, F.; Nicotra, F. Lipid A antagonists with anti-septic shock, antiinflammatory, anti-ischemia and analgesic activity. PCT/EP2007/002279.
34. Bettoni, I.; Comelli, F.; Rossini, C.; Granucci, F.; Giagnoni, G.; Peri, F.; Costa, B. Glial TLR4 Receptor as New Target to Treat Neuropatic Pain: Efficacy of a New Receptor Antagonist in A Model of Peripheral Nerve Injury in Mice Glia, 2008, 56, 1312-1319.
35. Piazza, M.; Yu, L.; Teghanemt, A.; Gioannini, T.; Weiss, J.; Peri, F. Evidence of a specific interaction between new synthetic antisepsis agents and CD14 Biochemistry, 2009, 48, 12337-44.
36. Seitz, O. Glycopeptide Synthesis and the Effects of Glycosylation on Protein Structure and Activity. ChemBiochem, 2000, 1, 214-246.
37. Blixt, O.; Allin, K.; Pereira, L.; Datta, A.; Paulson, JC. Efficient chemoenzymatic synthesis of O-linked sialyl oligosaccharides. J. Am. Chem. Soc., 2002, 124, 5739-5746.
38. Ramos, D.; Rollin, P.; Klaffke, W. Enzymatic Synthesis of Neo glycopeptide Building Blocks Angew. Chem. Int. Ed., 2000, 39, 396-398.
39. Meinjohanns, E.; Meldal, M.; Paulsen, H.; Dwek, R.A.; Bock, K.Novel sequential solid-phase synthesis of N-linked glycopeptides from natural sources. J. Chem. Soc. Perkin Trans. 1, 1998, 549-560.
40. Tiefenbrunn, T.K.; Dawson, P.E. Chemoselective ligation techniques: Modern applications of time-honored chemistry. Biopolymers, 2010, 94, 95-106;
41. Hackenberger, C.P.R.; Schwarzer, D. Chemoselective ligation and modification strategies for peptides and proteins. Angew. Chem., Int. Ed., 2008, 47, 10030-74;
42. Peri, F.; Nicotra, F. Chemoselective ligation in glycochemistry. Chem. Commun., 2004, 623-627.
43. Cervigni, S.E.; Dumy, P.; Mutter, M. Synthesis of glycopeptides and lipopeptides by chemoselective ligation. Angew. Chem., Int. Ed., 1996, 35, 1230-1232.
44. Peri, F.; Dumy, P.; Mutter, M. Chemo-and Stereoselective Glycosilation of hydroxylamino Derivatives: A Versatile Approach to Glycoconjugates Tetrahedron, 1998, 54, 12269-12278.
45. Carrasco, M.R.; Silva, O.; Rawls, K.A.; Sweeney, M.S.; Lombardo, A.A. Chemoselective alkylation of N-alkylaminooxy containing peptides. Org. Lett., 2006, 8, 3529-3532;
46. Carrasco, M.R.; Brown, R.T.; Doan, V.H.; Kandel, S.M.; Lee, Franklin C. 2- (N-Fmoc)-3-(N-Boc-N-methoxy)-diaminopropanoic acid, an amino acid for the synthesis of mimics of O-linked glycopeptides. Biopolymers, 2006, 84, 414-420;
47. Carrasco, M.R.; Nguyen, M.J.; Burnell, D.R.; MacLaren, M.D.; Hengel, S.M. Synthesis of neogly copeptides by chemoselective reaction of carbohydrates with peptides containing a novel N'-methyl-aminooxy amino acid. Tetrahedron Lett., 2002, 43, 5727-5729.
48. Peri, F.; Venturini, S.; Papini, A. M., unpublished results.
49. Jung, K.H.; Müller, M.; Schmidt, R.R. Intramolecular O-glycoside bond formation. Chem. Rev., 2000, 100, 4423-4442.
50. Seeberger, P.H.; Haase, W.-C. Solid-Phase Oligosaccharide Synthesis and Combinatorial Carbohydrate Libraries Chem. Rev., 2000, 100, 4349-4393.
51. Peri, F.; Deutman, A.; La Ferla, B.; Nicotra, F. Solution and solid-phase chemoselective synthesis of (1-6) amino(methoxy) di-and trisaccharide analogues Chem. Commun., 2002, 1504-1505.
52. Peri, F.; Jiménez-Barbero, J.; García-Aparicio, V.; Tvaroska, I.; Nicotra, F. Synthesis and conformational analysis of novel N(OCH3)-linked disaccharide analogues Chemistry, 2004, 10, 1433-1444.
53. Meezan, E.; Wu, H.C.; Black, P.H.; Robbins, P.W. Comparative Studies on the Carbohydrate-containing membrane components of normal and virus-transformed mouse fibroblasts. II. Separation of glycoproteins and glycopeptides by Sephadex chromatography. Biochemistry, 1969, 8, 2518-2524.
54. Hakomori, S. Glycosylation defining cancer malignancy: new wine in an old bottle. Proc. Natl. Acad. Sci. 2002, 99, 10231-3
55. Buskas, T.; Thompson, P.; Boons, G.J. Immunotheraphy for cancer: synthetic carbohydrate-based vaccines. Chem. Commun., 2009, 5335-5349.
56. Cipolla, L.; Peri, F.; Airoldi, C. Glycoconjugates in cancer therapy. Anti-Cancer Agents Med. Chem., 2008, 8, 92-121.
57. Peri, F.; Cipolla, L.; Rescigno, M.; La Ferla, B.; Nicotra, F. Synthesis and biological evaluation of an anticancer vaccine containing the C-glycoside analogue of the Tn epitope Bioconjug. Chem., 2001, 12, 325-328.
58. Cipolla, L.; Rescigno, M.; Leone, M.; Peri, F.; La Ferla, B.; Nicotra, F. Novel Tn antigen containing neoglycopeptides: synthesis and evaluation as antitumour vaccines Bioorg. Med. Chem., 2002, 10, 1639-1646.
59. Springer, G.F. T and Tn, general carcinoma autoantigens. Science, 1984, 224, 1198-206.
60. Hakomori, S. Possible functions of tumor-associated carbohydrate antigens. Curr. Opin. Immunol., 1991, 3, 646-653.
61. Hanessian, S. Total Synthesis of Natural Products: The Chiron Approach, Baldwin, J.E. Ed. Pergamon, Oxford, 1983.
62. Hollingsworth, R.I.; Wang, G. Toward a carbohydrate based chemistry: progress in the development of general purpose chiral synthons from carbohydrates. Chem. Rev., 2000, 100, 4267-82;
63. Meutermans, W.; Le, G.T.; Becker, B. Carbohydrates as Scaffolds in Drug Discovery. ChemMedChem, 2006, 1, 1164-1164.
64. Hirschmann, R.F., Nicolaou, K.C., Angeles, A.R. Chen, J.S.; Smith A.B. The -D-Glucose scaffold as a turn mimetic. Acc. Chem. Res., 2009, 42, 1511-1520.
65. Gruner, S.A.W.; Locardi, E.; Lohof, E.; Kessler, H. Carbohydrate- Based Mimetics in Drug Design: Sugar Amino Acids and Carbohydrate Scaffolds. Chem. Rev., 2002, 102, 491-514.
66. Gellman, S.H. Foldamers: A Manifesto Acc. Chem. Res., 1998, 31, 173-180.
67. Cipolla, L.; Peri, F.; La Ferla, B.; Redaelli, C.; Nicotra, F. Glycidic Scaffolds for the Production of Bioactive Compounds. Curr. Org. Synth., 2005, 2, 153-173.
68. Schweizer F. Glycosamino acids: Building Blocks for combinatorial Synthesis, Implications for Drug Discovery. Angew. Chem. Int. Ed., 2002, 41, 230-253;
69. Murphy, P.V.; Dunne, J.L.; Synthesis of peptidomimetics based on pyranose and polyhydroxylated piperidine scaffolds. Curr. Org. Synth., 2006, 3, 403-437;
70. Jensen, K.J.; Brask, J. Carbohydrates in protein and peptide design. Biopolymers, 2005, 80, 747-761;
71. Schweizer, F. In Handbook of Carbohydrate Engineering- Engineering carbohydrates into the side-chains of amino acids and use in combinatorial synthesis. Yarema, K.J. Ed.; CRC Press, Taylor & Francis Group: Boca Raton, 2005, pp. 749-779.
72. Lohof, E.; Planker, E.; Mang, C.; Burkhart, F.; Dechantsreiter, M.A.; Haubner, R.; Wester, H.-J; Schwaiger, M.; Hölzemann, G.; Goodman, S.L.; Kessler, H., Carbohydrate Derivatives for Use in Drug Design: Cyclic alpha(v)-Selective RGD Peptides Angew. Chem. Int. Ed., 2000, 39, 2761-2764;
73. Boer, J.; Gottschling, D.; Schuster, A.; Holzmann, B.; Kessler, H., Design, Synthesis, and Biological Evaluation of alpha(4)beta(1) Integrin Antagonists Based on beta-D-Mannose as Rigid Scaffold. Angew. Chem. Int. Ed., 2001, 40, 3870-3873;
74. Haubner, R.; Wester, H.-J.; Burkhart, F.; Senekowitsch-Schmidtke, R.; Weber, W.; Goodman, S.L.; Kessler, H.; Schwaiger, M., Glycosylated RGD-containing peptides: tracer for tumor targeting and angiogenesis imaging with improved biokinetics. J. Nucl. Med., 2001, 42, 326-336.
75. Hirschmann, R.; Yao, W.; Cascieri, M.A.; Strader, C.D.; Maechler, L.; Cichy-Knight, M.A.; Hynes, J. Jr; van Rijn, R.D.; Sprengeler, P.A.; Smith, A.B. Synthesis of potent cyclic hexapeptide NK-1 antagonists. Use of a minilibrary in transforming a peptidal somatostatin receptor ligand into an NK-1 receptor ligand via a polyvalent peptidomimetic. J. Med. Chem., 1996, 39, 2441-2448;
76. Hirschmann, R.; Hynes, J.Jr.; Cichy-Knight, M.A.; van Rijn, R.D.; Sprengeler, P.A.; Spoors, P.G.; Shakespeare, W.C.; Pietranico-Cole, S.; Barbosa, J.; Liu, J.; Yao, W.; Rohrer, S.; Smith, A. B. Modulation of receptor and receptor subtype affinities using diastereomeric and enantiomeric monosaccharide scaffolds as a means to structural and biological diversity. A new route to ether synthesis. J. Med. Chem., 1998, 41, 1382-1391.
77. Edwards, A.A.; Alexander, B.D.; Fleet, G.W.; Tranter, G.E., Spectroscopic studies of oligomers containing 2,5-trans furanoid sugar amino acids. Chirality, 2008, 20, 969-972.
78. Peri, F.; Bassetti, R.; Caneva, E.; De Gioia, L.; La Ferla, B.; Presta, M.; Tanghetti, E.; Nicotra, F. Arabinose-derived bicyclic amino acids: synthesis, conformational analysis and construction of an v 3-selective RGD peptide. J. Chem. Soc. Perkin Trans. I, 2002, 5, 638-644.
79. Araújo, A.C.; Nicotra, F.; Costa, B.; Giagnoni, G.; Cipolla, L. Fructose-fused -butyrolactones and lactams - synthesis and biological evaluation as GABA receptor ligands. Carbohydr. Res., 2008, 343, 1840-1848.
80. Araújo, A.C.; Nicotra, F.; Airoldi, C.; Costa, B.; Giagnoni, G.; Fumagalli, P.; Cipolla, L. Synthesis and Biological Evaluation of Novel Rigid 1,4-Benzodiazepine-2,5-dione Chimeric Scaffolds. Eur. J. Org. Chem., 2008, 635-639.
81. Farrant, M.; Nusser, Z. Variations on an inhibitory theme: phasic and tonic activation of GABAA receptors Nat. Rev. Neurosci., 2005, 6, 215-229.
82. Atack, J. R. Neurobiology of Memory and Anxiety: From Genes to Behavior. Exp. Opin. Invest. Drugs, 2005, 14, 601-8.
83. Cryan, J. F.; Kaupmann, K. Don't worry 'B' happy: A role for GABA receptors in anxiety and depression. Trends Pharmacol. B Sci., 2004, 26, 36-43.
84. Kalueff, A. V. Mapping convulsants' binding to the GABA-A receptor chloride ionophore: A proposed model for channel binding sites. Neurochem. Int., 2007, 50, 61-68.
85. Wittinghofer, A.; Waldmann, H. Ras: a molecular switch involved in tumor formation Angew. Chem., Int. Ed., 2000, 39, 4192-14.
86. Downward, J., Targeting RAS signalling pathways in cancer therapy. Nat Rev Cancer, 2003, 3, 11-22;
87. Krengel, U.; Schlichting, I.; Scherer, A.; Schumann, R.; Frech, M.; John, J.; Kabsch, W.; Pai, E.F.; Wittinghofer, A. Three-dimensional structures of H-ras p21 mutants: molecular basis for their inability to function as signal switch molecules. Cell, 1990, 62, 539-548.
88. Ganguly, A.; Pramanik, B.; Huang, E.; Liberles, S.; Heimark, L.; Liu, Y.; Tsarbopoulos, A.; Doll, R.; Taveras, A.; Remiszewski, S.; Snow, M.; Wang, Y.; Vibulbhan, B.; Cesarz, D.; Brown, J.; del Rosario, J.; James, L.; Kirschmeier, P.; Girijavallabhan, V., Detection and structural characterization of ras oncoprotein inhibitors complexes by electrospray mass spectrometry. Bioorg. Med. Chem., 1997, 5, 817-820;
89. Taveras, A.G.; Remiszewski, S.W.; Doll, R.J.; Cesarz, D.; Huang, E.C.; Kirschmeier, P.; Pramanik, B.N.; Snow, M.E.; Wang, Y.S.; del Rosario, J.D.; Vibulbhan, B.; Bauer, B.B.; Brown, J.E.; Carr, D.; Catino, J.; Evans, C.A.; Girijavallabhan, V.; Heimark, L.; James, L.; Liberles, S.; Nash, C.; Perkins, L.; Senior, M.M.; Tsarbopoulos, A.; Ganguly, A. K; Aust, R.; Brown, E.;Delisle, D.; Fuhrman, S.; Hendrickson, T.; Kissinger, C.; Love, R.; Sisson, W.; Villafranca, E.; Webber, S. E. Ras oncoprotein inhibitors: the discovery of potent, ras nucleotide exchange inhibitors and the structural determination of a drug-protein complex. Bioorg. Med. Chem., 1997, 5, 125-133;
90. Ganguly, A.K.; Wang, Y-S; Pramanik, B.N.; Doll, R.J.; Snow, M.E.; Taveras, A.G.; Remiszewski, S.; Cesarz, D.; del Rosario, J.; Vibulbhan, B.; Brown, J.E.; Kirschmeier, P.; Huang, E.C.; Heimark, L.; Tsarbopoulos, A., Girijavallabhan, V. M.; Aust, R. M.; Brown, E. L.; DeLisle, D. M.; Fuhrman, S. A.; Hendrickson, T. F.; Kissinger, C.R.; Love, R.A.; Sisson, W.A.; Villafranca, J.E.; Webber, S.E. Interaction of a novel GDP exchange inhibitor with the Ras protein. Biochemistry, 1998, 37, 15631-15637.
91. Colombo, S.; Peri, F.; Tisi, R.; Nicotra, F.; Martegani, E. Design and Characterization of a new class of Inhibitors of Ras activation Ann. NY Acad. Sci., 2004, 1030, 52-61.
92. Peri, F.; Airoldi, C.; Colombo, S.; Martegani, E.; van Neuren, A. S.; Stein, M.; Marinzi, C.; Nicotra, F. Design, Synthesis and Biological Evaluation of Sugar-Derived Ras Inhibitors ChemBiochem, 2005, 6, 1839-1848.
93. Airoldi, C.; Palmioli, A.; D'Urzo, A.; Colombo, S.; Vanoni, M.; Martegani, E.; Peri, F. Glucose-derived Ras pathway inhibitors: evidence of Ras-ligand binding and Ras-GEF (Cdc25) interaction inhibition, ChemBioChem, 2007, 8, 1376-1379.
94. Palmioli, A.; Sacco, E.; Abraham, S.; Thomas, C.J.; Di Domizio, A.; De Gioia, L.; Gaponenko, V.; Vanoni, M.; Peri F. First experimental identification of Ras-inhibitor binding interface using a water-soluble Ras ligand Bioorg. Med. Chem. Lett., 2009, 19, 4217-4222.
95. Peri, F.; Airoldi, C.; Colombo, S.; Mari, S.; Jiménez-Barbero, J.; Martegani, E.; Nicotra, F. Sugar-derived Ras inhibitors: group epitope mapping by NMR spectroscopy and biological evaluation. Eur. J. Org. Chem., 2006, 3707-3720.
96. Palmioli, A.; Sacco, E.; Airoldi, C.; Di Nicolantonio, F.; D'Urzo, A.; Shirasawa, S.; Sasazuki; T.; Di Domizio, A.; De Gioia, L.; Martegani, E.; Bardelli, A.; Peri, F.; Vanoni, M. Selective cytotoxicity of a byclic Ras inhibitor in cancer cells expressing K- RasG13D. Biochem. Biophys. Res. Commun., 2009, 386, 593-597.