title: The third dimension of reading the sugar code by lectins: design of glycoclusters with cyclic scaffolds as tools with the aim to define correlations between spatial presentation and activity.
abstract: Coding of biological information is not confined to nucleic acids and proteins. Endowed with the highest level of structural versatility among biomolecules, the glycan chains of cellular glycoconjugates are well-suited to generate molecular messages/signals in a minimum of space. The sequence and shape of oligosaccharides as well as spatial aspects of multivalent presentation are assumed to underlie the natural specificity/selectivity that cellular glycans have for endogenous lectins. In order to eventually unravel structure-activity profiles cyclic scaffolds have been used as platforms to produce glycoclusters and afford valuable tools. Using adhesion/growth-regulatory galectins and the pan-galectin ligand lactose as a model, emerging insights into the potential of cyclodextrins, cyclic peptides, calixarenes and glycophanes for this purpose are presented herein. The systematic testing of lectin panels with spatially defined ligand presentations can be considered as a biomimetic means to help clarify the mechanisms, which lead to the exquisite accuracy at which endogenous lectins select their physiological counterreceptors from the complexity of the cellular glycome.
authors.affiliation: School of Chemistry, National University of Ireland Galway, University Road, Galway, Ireland. paul.v.murphy@nuigalway.ie
authors.forename: Paul V
authors.initials: PV
authors.lastname: Murphy
authors.forename: Sabine
authors.initials: S
authors.lastname: André
authors.forename: Hans-Joachim
authors.initials: HJ
authors.lastname: Gabius
mesh_terms: D047250:Calixarenes / Q000737:chemistry; D003505:Cyclodextrins / Q000737:chemistry; D037161:Galectins / Q000737:chemistry*; D006001:Glycoconjugates / Q000737:chemistry; D007785:Lactose / Q000737:chemistry; D008024:Ligands; D008958:Models, Molecular; D009844:Oligosaccharides / Q000737:chemistry; D011134:Polysaccharides / Q000737:chemistry
chemical_list: D003505:Cyclodextrins; D037161:Galectins; D006001:Glycoconjugates; D008024:Ligands; D009844:Oligosaccharides; D011134:Polysaccharides; D047250:Calixarenes; D007785:Lactose
references.citation: FEBS J. 2006 Oct;273(19):4377-89
references.pmid: 16956372
references.citation: Bioconjug Chem. 2009 Sep;20(9):1716-28
references.pmid: 19715307
references.citation: Histol Histopathol. 2012 Apr;27(4):397-416
references.pmid: 22374719
references.citation: J Biol Chem. 1990 May 15;265(14):7864-71
references.pmid: 2335508
references.citation: Biochem Biophys Res Commun. 1971 Nov 5;45(3):622-9
references.pmid: 5128172
references.citation: Biol Chem. 2009 Jul;390(7):557-65
references.pmid: 19426132
references.citation: FEBS J. 2012 Nov;279(21):4062-80
references.pmid: 22943525
references.citation: J Org Chem. 2002 May 3;67(9):3057-64
references.pmid: 11975567
references.citation: Org Biomol Chem. 2011 Aug 7;9(15):5445-55
references.pmid: 21660340
references.citation: Chem Commun (Camb). 2011 Jun 7;47(21):6126-8
references.pmid: 21523264
references.citation: Glia. 2001 Mar 1;33(3):241-55
references.pmid: 11241742
references.citation: Glycobiology. 2012 Sep;22(9):1207-17
references.pmid: 22547138
references.citation: Virchows Arch B Cell Pathol Incl Mol Pathol. 1986;52(2):107-15
references.pmid: 2878527
references.citation: ACS Chem Biol. 2012 Jan 20;7(1):31-43
references.pmid: 22195988
references.citation: Histol Histopathol. 2010 May;25(5):541-50
references.pmid: 20238293
references.citation: Nat Prod Rep. 2012 Aug;29(8):899-934
references.pmid: 22729238
references.citation: Anat Rec (Hoboken). 2011 Mar;294(3):427-44
references.pmid: 21290613
references.citation: Naturwissenschaften. 2000 Mar;87(3):108-21
references.pmid: 10798195
references.citation: Analyst. 2011 Dec 21;136(24):5270-6
references.pmid: 22016878
references.citation: J Org Chem. 2009 Dec 4;74(23):9010-26
references.pmid: 19899775
references.citation: Org Biomol Chem. 2003 Nov 21;1(22):3909-16
references.pmid: 14664382
references.citation: J Biochem. 1996 Jan;119(1):1-8
references.pmid: 8907168
references.citation: Biochemistry. 2009 May 26;48(20):4403-16
references.pmid: 19344160
references.citation: Glycobiology. 2012 Apr;22(4):470-8
references.pmid: 22025012
references.citation: J Biol Chem. 1996 May 31;271(22):12744-8
references.pmid: 8662681
references.citation: Biochim Biophys Acta. 1983 Dec 27;761(3):237-45
references.pmid: 6197094
references.citation: Nat Genet. 2005 Jul;37(7):692-700
references.pmid: 15924140
references.citation: J Biol Chem. 2005 Nov 4;280(44):37266-77
references.pmid: 16105842
references.citation: Diabetes. 2011 Sep;60(9):2341-9
references.pmid: 21788572
references.citation: Org Biomol Chem. 2012 Sep 14;10(34):6893-907
references.pmid: 22842468
references.citation: J Mol Biol. 2004 Oct 29;343(4):957-70
references.pmid: 15476813
references.citation: Glycobiology. 2005 Aug;15(8):805-17
references.pmid: 15843597
references.citation: Curr Opin Genet Dev. 2007 Jun;17(3):245-51
references.pmid: 17467977
references.citation: Angew Chem Int Ed Engl. 2004 May 3;43(19):2518-21
references.pmid: 15127440
references.citation: Biochemistry. 1990 Jun 5;29(22):5315-9
references.pmid: 1696497
references.citation: Org Biomol Chem. 2009 Nov 21;7(22):4715-25
references.pmid: 19865709
references.citation: Graefes Arch Clin Exp Ophthalmol. 2012 Aug;250(8):1169-80
references.pmid: 22527325
references.citation: Bioconjug Chem. 2001 Sep-Oct;12(5):655-72
references.pmid: 11562183
references.citation: Histol Histopathol. 2003 Jul;18(3):771-9
references.pmid: 12792889
references.citation: Cell Mol Life Sci. 1999 Mar;55(3):368-422
references.pmid: 10228555
references.citation: Trends Biochem Sci. 2011 Jun;36(6):298-313
references.pmid: 21458998
references.citation: J Cell Biol. 2005 May 9;169(3):491-501
references.pmid: 15883199
references.citation: Chemistry. 2002 May 03;8(9):1982-90
references.pmid: 11981882
references.citation: Neurochem Res. 2012 Jun;37(6):1267-76
references.pmid: 22234579
references.citation: Biochemistry. 1984 Aug 28;23(18):4255-61
references.pmid: 6487600
references.citation: Philos Trans R Soc Lond B Biol Sci. 2012 Sep 19;367(1602):2513-6
references.pmid: 22889903
references.citation: Biochim Biophys Acta. 2006 May;1760(5):768-82
references.pmid: 16581187
references.citation: Acc Chem Res. 2001 Jan;34(1):18-29
references.pmid: 11170353
references.citation: J Biol Chem. 1974 Sep 10;249(17):5536-43
references.pmid: 4370480
references.citation: Org Lett. 2001 Aug 23;3(17):2629-32
references.pmid: 11506595
references.citation: Biochemistry. 2005 Sep 20;44(37):12564-71
references.pmid: 16156668
references.citation: Histopathology. 2011 Mar;58(4):543-56
references.pmid: 21410745
references.citation: Gastroenterology. 2009 Apr;136(4):1379-90, e1-5
references.pmid: 19171142
references.citation: Biochimie. 2004 Apr-May;86(4-5):317-26
references.pmid: 15194236
references.citation: Bioorg Med Chem Lett. 2012 Jan 1;22(1):313-8
references.pmid: 22142540
references.citation: Carbohydr Res. 2005 May 23;340(7):1437-40
references.pmid: 15854619
references.citation: Expert Opin Ther Targets. 2013 Apr;17(4):379-92
references.pmid: 23289445
references.citation: FEBS J. 2007 Jul;274(13):3233-56
references.pmid: 17535296
references.citation: J Biol Chem. 2001 Sep 21;276(38):35917-23
references.pmid: 11451961
references.citation: Glycoconj J. 2013 Jan;30(1):5-10
references.pmid: 22527830
references.citation: Chembiochem. 2008 Jul 2;9(10):1649-61
references.pmid: 18509838
references.citation: Glycobiology. 2002 Apr;12(4):43R-56R
references.pmid: 12042244
references.citation: Glycobiology. 1996 Dec;6(8):843-9
references.pmid: 9023547
references.citation: Biochem J. 2008 Jan 15;409(2):591-9
references.pmid: 17887955
references.citation: Chem Rev. 1998 Apr 2;98(2):637-674
references.pmid: 11848911
references.citation: Ann N Y Acad Sci. 2012 Apr;1253:206-21
references.pmid: 22524425
references.citation: J Biol Chem. 1983 Jan 10;258(1):199-202
references.pmid: 6848494
references.citation: Cancer. 1988 Mar 15;61(6):1125-31
references.pmid: 2449274
references.citation: J Immunol. 2009 Apr 1;182(7):4036-45
references.pmid: 19299701
references.citation: Biochim Biophys Acta. 2002 Sep 19;1572(2-3):165-77
references.pmid: 12223267
references.citation: IUBMB Life. 2010 Aug;62(8):624-8
references.pmid: 20665623
references.citation: Traffic. 2009 Apr;10(4):438-50
references.pmid: 19192249
references.citation: Histochem Cell Biol. 2011 Jun;135(6):539-52
references.pmid: 21584695
references.citation: J Biol Chem. 2004 Mar 19;279(12):10841-7
references.pmid: 14672941
references.citation: Carbohydr Res. 2012 Jul 15;356:132-41
references.pmid: 22391124
references.citation: J Biol Chem. 2008 Jul 18;283(29):20547-59
references.pmid: 18456665
references.citation: Anticancer Res. 2012 May;32(5):1565-72
references.pmid: 22593433
references.citation: Phytochemistry. 2011 Jul;72(10):975-96
references.pmid: 21353264
references.citation: Anticancer Res. 1989 May-Jun;9(3):723-30
references.pmid: 2764517
references.citation: Biosci Biotechnol Biochem. 2008 May;72(5):1155-67
references.pmid: 18460788
references.citation: Glycobiology. 2011 Dec;21(12):1627-41
references.pmid: 21712397
references.citation: FEBS J. 2010 Sep;277(17):3552-63
references.pmid: 20695889
references.citation: Eur J Cancer. 1994;30A(5):653-7
references.pmid: 8080681
references.citation: Glycoconj J. 2010 Feb;27(2):211-25
references.pmid: 19888650
references.citation: Chem Biol. 2007 Oct;14(10):1140-51
references.pmid: 17961826
references.citation: Biochim Biophys Acta. 2002 Sep 19;1572(2-3):209-31
references.pmid: 12223271
references.citation: Eur J Biochem. 2004 Jan;271(1):118-34
references.pmid: 14686925
references.citation: Mol Biosyst. 2010 Oct;6(10):1773-81
references.pmid: 20556308
references.citation: J Med Chem. 2002 Jan 17;45(2):478-91
references.pmid: 11784152
references.citation: J Biol Chem. 1977 Aug 10;252(15):5444-8
references.pmid: 560374
references.citation: Glycobiology. 2006 Dec;16(12):158R-184R
references.pmid: 16973733
references.citation: J Am Chem Soc. 2004 Sep 29;126(38):11914-22
references.pmid: 15382926
references.citation: Bioorg Med Chem. 2011 May 15;19(10):3280-7
references.pmid: 21524586
references.citation: Biochim Biophys Acta. 2002 Sep 19;1572(2-3):232-54
references.pmid: 12223272
references.citation: Mol Biosyst. 2009 Oct;5(10):1087-104
references.pmid: 19756298
references.citation: J Biol Chem. 1987 May 25;262(15):7383-90
references.pmid: 2438278
references.citation: Bioconjug Chem. 2004 Jan-Feb;15(1):87-98
references.pmid: 14733587
references.citation: Biochim Biophys Acta. 2011 Feb;1810(2):150-61
references.pmid: 21070836
references.citation: Glycobiology. 1999 Nov;9(11):1253-61
references.pmid: 10536041
references.citation: Histol Histopathol. 1993 Apr;8(2):369-83
references.pmid: 8490266
references.citation: Biochimie. 2012 Dec;94(12):2649-55
references.pmid: 22884463
references.citation: Annu Rev Biochem. 1986;55:287-315
references.pmid: 3527044
references.citation: J Biol Chem. 1980 May 10;255(9):4236-9
references.pmid: 6768752
references.citation: Nat Rev Mol Cell Biol. 2012 Jun 22;13(7):448-62
references.pmid: 22722607
references.citation: Angew Chem Int Ed Engl. 2000 Dec 1;39(23):4348-4352
references.pmid: 29711903
references.citation: Eur J Biochem. 1997 Oct 1;249(1):27-38
references.pmid: 9363750
references.citation: Chemistry. 2013 Feb 4;19(6):1896-902
references.pmid: 23280962
references.citation: Int J Biochem Cell Biol. 2010 Jun;42(6):1019-29
references.pmid: 20227520
references.citation: J Pept Sci. 2011 Jun;17(6):427-37
references.pmid: 21294229
references.citation: Biochemistry. 2007 Jun 12;46(23):6984-95
references.pmid: 17497937