Synthetic methods of glycopeptide assembly, and biological analysis of glycopeptide products

Current Opinion in Chemical Biology

Volumn 1, Issue 4, 1997, Pages 552-563

  Meldal, Morten ^a   St Hilaire, Phaedria M ^a  

^a CARLSBERG LABORATORY   (Denmark)

Author keywords

[No Author keywords available]

Indexed keywords

GLYCOPEPTIDE; HLA ANTIGEN CLASS 2; LYMPHOCYTE ANTIGEN RECEPTOR; OLIGOSACCHARIDE; PEPTIDE LIBRARY; SIALOGLYCOPROTEIN;

AMINO ACID SEQUENCE; ANIMAL; CARBOHYDRATE ANALYSIS; CHEMICAL STRUCTURE; CHEMISTRY; CONFORMATION; HUMAN; MAJOR HISTOCOMPATIBILITY COMPLEX; METABOLISM; MOLECULAR GENETICS; REVIEW; SYNTHESIS;

AMINO ACID SEQUENCE; ANIMALS; CARBOHYDRATE CONFORMATION; CARBOHYDRATE SEQUENCE; GLYCOPEPTIDES; HISTOCOMPATIBILITY ANTIGENS CLASS II; HUMANS; MAJOR HISTOCOMPATIBILITY COMPLEX; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; OLIGOSACCHARIDES; PEPTIDE LIBRARY; RECEPTORS, ANTIGEN, T-CELL; SIALOGLYCOPROTEINS;

EID: 0031323343     PISSN: 13675931     EISSN: None     Source Type: Journal    
DOI: 10.1016/S1367-5931(97)80052-X     Document Type: Article

References (115)

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41. N. Carbohydr Res 1997, 299:33-48. The synthesis of the 18-mer amino-terminal fragment of glycophorin A carrying nine saccharides attached to consecutive threonines and serines was achieved. The multi-glycosylated product was completely assigned by proton nuclear magnetic resonance spectroscopy and interesting structural features resulting from the glycan-threonine linkage were identified by nuclear Overhauser effect (NOE) experiments.
42. 2. Ligand binding to mannan-bind ing proteins (MBPs). Bioorg Med Chem 1996, 4:1881-1899. The authors describe a new method for the computational design and preparation of multiantennary high mannose oligosaccharides mimics. The ligands were evaluated for their ability to inhibit mannan-binding protein (MBP) binding to polymannan. Both the high mannose oligosaccharides and the mimics, however, were unable to inhibit the binding of mannan, indicating the special character of multivalency displayed by the bouquet-shaped MBP.
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47. Mathieux N, Paulsen H, Meldal M, Bock K: Synthesis of glycopeptide sequences of repeating units of the MUC2 and MUC3 containing oligosaccharide side chains with core 1, core 2, core 3, core 4 and core 6 structure. J Chem Soc Perkin Trans 1 1997:2359-2368. In this work all the relevant core structure building blocks were prepared and used in the synthesis of a large series of MUC2 and MUC3 glycopeptides using multiple column techniques. These compounds are extremely interesting for biochemical studies of the course and effects of mucin glycosylation.
48. Meinjohanns E, Meldal M, Jensen T, Werdelin O, Galli-Stampino L, Mouritsen S, Bock K: Versatile solid-phase thiolytic reduction of azido and N-Dts groups in the synthesis of haemoglobin (67-76) O-glycopeptides and photoaffinity labelled analogs to study glycan T-cell specificity. J Chem Soc Perkin Trans 1 1997:871-884. Dithiothreitol-mediated thiolytic reductions of azido and dithiasuccinoyl groups to free amines on solid phase were reported for the first time. Solid phase reduction of azides are quite important since many modified amino acid and glycosyl amino acid analogs are prepared via azido intermediates.
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57. Meinjohanns E, Vargas-Berenguel A, Meldal M, Bock K: Comparison of N-Dts and N-Aloc in the solid-phase syntheses of O-GlcNAc glycopeptide fragments of RNA-polymerase II and mammalian neurofilaments. J Chem Soc Perkin Trans 1 1995:2165-2175.
58. Jensen KJ, Hansen PR, Venugopal D, Barany G: Synthesis of 2-acetamido-2-deoxy-D-glucopyranose O-glycopeptides from N-dithiasuccinoyl-protected derivatives. J Am Chem Soc 1996, 118:3148-3155.
59. Broddefalk J, Bergquist K-E, Kihlberg J: Preparation of a glycopeptide analogue of Type II collagen - use of acid labile protective groups for carbohydrate moieties in solid phase synthesis of O-linked glycopeptides. Tetrahedron Lett 1996, 37:3011-3014.
60. Nakahara Y, Ogawa T: Solid-phase synthesis of an O-linked glycopeptide based on a benzyl-protected glycan approach. Carbohydr Res 1996, 292:71-81.
61. Seitz O, Kunz H: Hycron, an allylic anchor for high-efficiency solid-phase synthesis of protected peptides and glycopeptides. J Org Chem 1997, 62:813-826. The Hycron allylic anchor attaches a polar spacer to nonpolar polystyrene in a similar manner to the conventional PEG-PS (polyethyleneglycol polystyrene) resins. The allylic anchor is orthogonal to the conventional protecting groups used in solid phase chemistry, thus the new anchor allows solid phase preparation and cleavage of fully protected glycopeptide fragments.
62. Meldal M, Meinjohanns E, Frische K, Jensen T, Hansen P, Werdelin O, Galli-Stampino L, Mouritsen S, Bock K: Libraries of synthetic glycopeptides in the characterization of the T-cell response to tumor associated mucin antigens. Proceedings of the 2nd Chinese Peptide Symposium 1997, in press.
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64. Woltering TJ, Weitz-Schmidt G, Wong C-H: C-fucopeptides as selectin antagonists: Attachment of lipid moieties enhances the activity. Tetrahedron 1996, 37:9033-9036. A range of monovalent peptides designed as setectin mimetics were synthesized and tested. These mimetics utilize L-fucose, D-galactose or D-mannose C- or O-linked to an amino acid with the trans-diol configuration that mimics the sialyl Lewis X antigen (SLex) galactose residue. A carboxylic acid-containing moiety was then attached to the glycopeptide. Most of these mimetics were more potent than SLex or the multivalent inhibitors designed. (See also Wu et al., 1996 [66], Cappi et al., 1997 [67], and Marron et al., 1996 [68]).
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66. Wu S-H, Shimazaki M, Lin C-C, Qiao L, Moree WJ, Weitz-Schmidt G, Wong C-H: Synthesis of fucopeptides as sialyl Lewis X mimetics. Angew Chem Int Ed 1996, 35:88-90.
67. Cappi MW, Moree WJ, Qiao L, Marron TG, Weitz SG, Wong C-H: Synthesis of novel 6-amido-6-deoxy-L-galactose derivatives as sialyl Lewis X mimetics. Bioorg Med Chem 1997, 5:283-296.
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69. Lin C-C, Shimazaki M, Heck M-P, Wang R, Kimura T, Ritzen H, Takayama S, Wu S-H, Weitz-Schmidt G, Wong C-H: Synthesis of sialyl Lewis X mimetics and related structures using the glycosyl phosphite methodology and evaluation of E-selectin inhibition. J Am Chem Soc 1996, 118:6826-6840. This paper contains comprehensive discussion of the synthesis and biological evaluation of various fucopeptides that mimic sialyl Lewis X antigen. The authors also present the use of glycosyl phosphites for generating both O- and C-linked glycosyl amino acids with an emphasis on stereoselectivity and anomeric reactivity.
70. n-glycosylated peptide antigens. Eur J Immunol 1996, 26:1342-1349. This paper presents the first complete characterization of all the important residues in the glycopeptide antigen T cell response. An array of glycopeptides based on the non-immunogenic VITAFNEGLK (single-letter amino acid code) sequence from mouse hemoglobin (67-76) substituted in all positions with serine, threonine, tyrosine, asparagine, serine(GalNAc) and threonine (GalNAc) were used in T cell proliferation studies to demonstrate that only a single position in the central part of the self-peptide permits glycosylation and that the resulting glycopeptides are highly immunogenic eliciting a carbohydrate-dependent T cell response.
71. Galli-Stampino L, Meinjohanns E, Frische K, Meldal M, Jensen T, Werdelin O, Mouritsen S: The nature of the glycan moiety plays a decisive role in determining glycopeptide immunogenicity. J Cancer Res 1997, 57:3214-3222. In this comprehensive investigation of the carbohydrate specificity of the T cell response to normal and cancer associated mucin, as well as to unrelated glycopeptide antigens, the authors found that the immune system recognizes mono- and disaccharides very well. The multiple histocompatibility complex (MHC)-binding affinity was virtually carbohydrate-independent. The mucin structures were particularly antigenic and there seemed to be a natural restriction on the T cell level for the structures characteristic of malignancy. The N-acetylgalactosamine (GalNAc) residue protrudes away from the peptide-MHC complex presenting the 4 and 6 position to the T cell receptor for key polar interactions.
72. Jensen T, Hansen P, Galli-Stampino L, Mouritsen S, Frische K, Meinjohanns E, Meldal M, Werdelin O: Carbohydrate- and peptide specificity of MHC class II restricted T cell hybridomas raised an O-glycosylated self-peptide. J Immunol 1997, 158:3769-3778. By establishing the hybridoma T cell lines that respond to the VITAFT (GalNAcEGLK) peptide, it was possible to study the fine specificity of T cell cross reactivity between different glycopeptides. It was found that each T cell receptor specifically recognized a single glycopeptide. Hybridomas that recognized the nonglycosylated peptide did not react with the glycopeptide, indicating that these hybridomas (<3%) were derived by glycopeptide processing. Only a single hybridoma showed cross reactivity to the very similar C-4 epimeric α-GlcNAc-peptide, in terms of binding and recognition.
73. Deck B, Elofsson M, Kihlberg J, Unanue ER: Specificity of glycopeptide-specific T cells. J Immunol 1995, 1074-1078.
74. Abdel-Motal UM, Berg L, Rosen A, Bengtsson M, Thorpe CJ, Kihlberg J, Dahmen J, Magnusson G, Karlsson K-A, Jondal M: Immunization with glycosylated Kb-binding peptides generates carbohydrate-specific, unrestricted cytotoxic T cells. Eur J Immunol 1996, 26:544-551. The authors report that carbohydrates spaced four bonds further away than the natural O-linked structures (by insertion of an ethylthiomethyl ether moiety) were able to generate peptide-independent cytolytic T cells which could release chromium from cells carrying the carbohydrate as an artificial glycolipid in the surface membrane. These results are extremely relevant for the design of cancer vaccines.
75. O'Donnell MJ, Zhou C, Scott WL: Solid-phase unnatural peptide synthesis (UPS). J Am Chem Soc 1996, 118:6070-6071.
76. 2 were used to characterize the specificity of polypeptide-α-N-acetylgalactosaminyltransferase. The transfer was highly dependent on prior glycosylation of proximal serine/threonine residues. Thr4 of the three consequetive threonines was the preferred glycosylation site followed by Thr3. Once glycosylated at Thr4 only Thr2 can be glycosylated with a much reduced rate. The results suggest that several transferases are required to obtain the naturally occurring highly glycosylated mucin structures. Such transferase families have indeed since been identified (Lectures at the Workshop on 'Mucin O-glycosylation: Sites and Processing', Vedbæk, Copenhagen, May 30th-June 1st 1997).
77. Jansson AM, Jensen KJ, Meldal M, Lomako J, Lomako WM, Olsen CE, Bock K: Solid phase glycopeptide synthesis of tyrosine glycosylated glycogenin fragments as substrates for glycosylation by glycogenin. J Chem Soc Perkin Trans 1 1996:1001-1006. The authors successfully achieved the glycosylation of tyrosine (normally a difficult glycosyaltion) yielding both the α- and β-linked building blocks of maltose and glucose. Several 25-mer glycopeptide fragments of the glycogen primer protein, glycogenin, were then synthesized. A study of the trnsfer of the glycosylated tyrosine to these substrates indicatedthat the β-anomer was preferentially transferred, suggesting that it is the natural substrate. The first self glycosylation was intramolecular and subsequent elongation involved a protein dimer complex with intermolecular glycosyl transfer.
78. Jansson AM, Jensen KJ, Meldal M, Bock K: Solid phase glycopeptide synthesis of tyrosine glycosylated glycogenin fragments. In Innovations and Perspectives in Solid Phase Synthesis. Edited by Epton R. Kingswindford: Mayflower Worldwide; 1997:423-426.
79. Hansen HC, Haataja S, Finne J, Magnusson G: Di-, tri, and tetravalent dendritic galabiosides that inhibit hemagglutination by Streptococcus suis at nanomolar concentration. J Am Chem Soc 1997, 119:6974-6979. The authors investigated the effects of multivalency, spacer length, flexibility of spacer and scaffold and spatial arrangement of ligand on the inhibition of bacterial adhesion by glycopeptide conjugates. These compounds also represent the first soluble saccharide bacterial adhesion inhibitors which are active in the nanomolar range.
80. Inazu T, Mizuno M, Maegami T, Haneda K: Solid-phase syntheses of N-glycopeptides and digestion of glycotetrapeptide by carboxypeptidase W. Pept Chem 1996, 34:41-44.
81. Live DH, Kumar Ra, Beebe X, Danishefsky SJ: Conformational influences of glycosylation of a peptide: a possible model for the effect of glycosylation on the rate of protein folding. Proc Natl Acad Sci USA 1996, 93:12759-12761.
82. Lee K-C, Falcone ML, Davis JT: Sequence-specific peptide-carbohydrate interactions in an asparagine-linked glycopeptide. J Org Chem 1996, 61:4198-4199.
83. Mer G, Hietter H, Lefecre J-F: Stabilization of proteins by glycosylation examined by NMR analysis of a fucosylated proteinase inhibitor. Nat Struct Biol 1996, 3:45-53.
84. Otvos L Jr, Cappelletto B, Varga I, Wade JD, Xiang ZQ, Kaiser K, Stephens LJ, Ertl HCJ: The effects of post-translational side-chain modifications on the stimulatory activity, serum stability and conformation of synthetic peptides carrying T helper cell epitopes. Biochim Biophys Acta 1996, 1313:11-19.
85. 2) chromophore enabled these glycopeptide to be used for the study of glycopeptide dynamics and the influence of glycosylation. Considerable destabilization of the leucine zipper was observed and this is thought to be due to glycosylation on the outside of the zipper dimer. Surprisingly, the rate of exchange of the more stable zipper dinners was on the order of several hours as measured by change of fluorescence intensity upon mixing of the labeled peptides.
86. O'Conner SE, Imperiali B: Conformational switching by asparagine-linked glycosylation. J Am Chem Soc 1997, 119:2295-2296. NMR spectroscopy of designed model glycopeptides indicates that N-linked glycosylation may induce a conformational change towards a β-turn structure similar to that frequently found at glycosylation sites in glycoproteins. This suggests that glycosylation may influence protein folding favorably.
87. O'Connor SE, Imperiali B: Modulation of protein structure and function by asparagine-linked glycosylation. Chem Biol 1996, 3:803-812.
88. Matsuda M, Nishimura SI: Synthesis of a cell adhesive glycopeptide. Pept Chem 1996, 33rd:381-384, 95.
89. Meldal M, Franzyk H, Meinjohanns E, Vargas-Berenguel A, Frische K, Christensen MK, Christiansen-Brams I, Jensen KJ, Bock K: Recent techniques in glycopeptide synthesis and biology: the glycopeptide templates. In Innovation and Perspectives Solid Phase Synthesis. Edited by Epton R. Kingswinford: Mayflower Worldwide; 1997:263-268.
90. Page D, Zanini D, Roy R: Macromolecular recognition: effect of multivalency in the inhibition of binding of yeast mannan to Concanavalin A and pea lectins by mannosylated dendrimers. Bioorg Med Chem 1996, 4:1949-1961. The effect of multivalency on the inhibition of concavalin A and pea lectin binding to yeast mannan was studied. The authors detail synthetic and biological evaluation of the dendritic inhibitors and conclude that optimum inhibitory power is a function of both lectin and dendrimer valencies.
91. Roy R, Saha UK: Rational design of multivalent glycoconjugate ligands. Synthesis of libraries of conformationally flexible rotamers of poly-N-linked lactosyl glycines. J Chem Soc Chem Commun 1996:201-202.
92. Cervigni SE, Dumy P, Mutter M: Synthesis of glycopeptides and lipopeptides by chemoselective ligation. Angew Chem Int Ed 1996, 35:1230-1232. The authors describe a chemoselective ligation of unprotected peptides, oligosaccharides and lipids to form glycopeptides and lipopeptides. Combined with an orthogonal protecting group strategy, this method lends ease and diversity to glycopeptidoconjugate synthesis.
93. Paulsen H, Schleyer A, Mathieux N, Meldal M, Bock K: A new solid-phase oligosaccharide synthesis on glycopeptides bound to a solid phase. J Chem Soc Perkin Trans 1 1997:281-293. The authors report the glycosylation of the oligosaccharide moiety of glycopeptides on solid phase stereoselectively and with high yield.
94. Schleyer A, Meldal M, Renil M, Paulsen H, Bock K: Direct solid-phase glycosylations of peptide templates on a novel PEG-based resin. Angew Chem Int Ed Engl 1997, 109:2064-2067. For the first time, glycosylation of peptide hydroxyl groups on solid phase was achieved. The success was ascribed to the application of a new polymer (Renil and Meldal (1996) [96]) containing alkyl ether bonds. A small glycopeptide library was constructed by two successive glycosylations of template mixtures in a combinatorial manner, and the products were characterized.
95. Meldal M, Renil M, Juliano MA, Jansson AM, Meinjohanns E, Buchardt J, Schleyer A: Novel PEG-based resins and synthetic methods: Azido acids in SPPS and direct solid-phase peptide glycosylations. In Peptides 1996, Proceedings of the European Peptide Symposioum. Edited by Epton R. Kingswinford: Mayflower Scientific; 1997:in press
96. Renil M, Meldal M: POEPOP and POEPS: Inert polyethylene glycol crosslinked polymeric supports for solid phase synthesis. Tetrahedron Lett 1996, 37:6185-6188.
97. Meldal M, Juliano MA, Jansson AM: Azido acids in a novel method of solid-phase peptide synthesis. Tetrahedron Lett 1997, 38:2531-2534.
98. Lay L, Meldal M, Nicotra F, Panza L, Russo G: Stereoselective synthesis of the C-analog of β-D-glucopyrannosyl serine. J Chem Soc Chem Commun 1997, in press.
99. Györgydeák Z, Szilágyi L, Paulsen H: Synthesis, structure and reactions of glycosyl azides. J Carbohydr Chem 1997, 12:139-163.
100. Meinjohanns E, Meldal M, Bock K; Efficient synthesis of O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-Ser/Thr building blocks for SPPS of O-GlcNac glycopeptides. Tetrahedron Lett 1995, 36:9205-9208.
101. Saha UK, Schmidt RR: Efficient synthesis of O-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-serine and threortine building blocks for glycopeptide formation. J Chem Soc Perkin Trans 1 1997:1855-1860.
102. Christiansen-Brams I, Jansson AM, Meldal M, Breddam K, Bock K: Silyl protection in the solid-phase synthesis of N-linked glycopeptides. Preparation of glycosylated fluorogenic substrates for subtilisins. Bioorg Med Chem 1994, 2:1153-1167.
103. Elofsson M, Roy S, Salvador LA, Kihlberg J: Building blocks for glycopeptide synthesis: preparation of α-O-fucosylated Fmoc serine and threonine in one step from L-fucose tetraacetate. Tetrahedron Lett 1996, 37: 7645-7648.
104. Ercegovic T, Magnusson G: Highly stereoselective α-sialylation. Synthesis of GM3-saccharide and a bis-sialic acid unit. J Org Chem 1995, 60:3378-3384.
105. Michaëlsson E, Broddefalk J, Engström Å, Kihlberg J, Holmdahl R: Antigen processing and presentation of a naturally glycosylated protein elicits major histocompatibility complex class II-restricted, carbohydrate-specific T cells. Eur J Immunol 1996, 26:1906-1910.
106. Kim JM, Roy R: New prototypical O-linked-glycopeptidomimetics corresponding to the linkage region of proteoglycans. Carbohydr Res 1997, 298:173-179.
107. Kim JM, Roy R: Oligomeric glycopeptidomimetics bearing the cancer related Tn-antigen. Tetrahedron Lett 1997, 38:3487-3490.
108. Ashton PR, Boyd S, Brown C, Jayaraman N, Stoddart F: A convergent synthesis of a carbohydrate-containing dendrimer. Angew Chem Int Ed 1997, 36:732-735. This work describes an impressive synthesis of a 36-mer glucodendrimer using the convergent approach. The limitations of convergent synthesis, with respect to steric hindrance and crowding of the interstitial space around the central core, come into play when two different convergent strategies (a 12 × 3 versus a 6 × 6 reaction sequence) are explored.
109. Zanini D, Roy R: Synthesis of new α-thiosialodendrimers and their binding properties to the sialic acid specific lectin from Limax flavus. J Am Chem Soc 1997, 119:2088-2095. The effect of multivalency and spatial arrangement on binding of a lectin to glycodendrimers was studied. The authors describe the synthesis of two types of branched sialylated glycodendrimers, and compare their biological activity in a range of in vitro assays. The difference in inhibitory power arose from rather small changes in the nature of the dendrimer central core and flexibility. Conformational differences between the two types of glycodendrimers, if there are any, have not yet been established. (See also Hansen et al. (1997) [79••]).
110. Löffler A, Doucey M-A, Jansson A, Müller DR, de Beer T, Hess D, Meldal M, Richter WJ, Vliegenhart JFG, Hofsteenge J: Spectroscopic and protein chemical analyses demonstrate the presence of C-mannosylated tryptophan in intact human RNase 2 and its isoforms. Biochemistry 1996, 35:12005-12014.
111. Singh DG, Lomako J, Lomako WM, Whelan WJ, Meyer HE, Serwe M, Metzger JW: β-Glucosylarginine: a new glucose-protein bond in a self-glucosylating protein from sweet corn. FEBS Lett 1995, 376:61-64.
112. Hoffmann M, Burkhart F, Hessler G, Kessler H: C-glycoside analogues of N4-(2-acetamido-2-deoxy-β-D-glucopyranosyl)-L-asparagine: synthesis and conformational analysis of a cyclic C-glycopeptide. Helv Chim Acta 1996, 79: 1519-1532. Glycosyl stannanes were used to construct C-linked glycopeptides of amino sugars with an inverted asparagine amide bond. The technique could be used in the stereoselective construction of C-linked aminoglycosyl amino acid derivatives.
113. Lee KB, Lee YC: Conformational studies of glycopeptides by energy transfer. Introduction of fluorophore at specific branches of biantennary glycopeptides The synthesis of C-glycoside inhibitors of cell surface carbohydrate receptors: exploiting the carbohydrates' stereochemical and connective diversity. J Biol Chem 1996, 271:1462-1469.
114. Michael K, Wittmann V, König W, Sandow J, Kessler H: S- and C-glycopeptide derivatives for an LH-RH agonist. Int J Pept Protein Res 1996, 48:59-70.
115. Burkhart F, Hoffmann M, Kessler H: Stereoselective synthesis of a C-glycosidic analog of N-glucoasparagine. Angew Chem Int Ed 1997, 36:1191-1192. Use of the glycosylstannane method (Hoffman et al. (1996) [112•] C-linked glycosyl amino acids were synthesized via the dilithiated intermediate and an amino acid derivative carrying a sidechain aldehyde. This is the first practical synthesis of a C-linked amino sugar amino acid derivative, and the method should be general for any sidechain length.