Solid Phase Libraries of Glycopeptide Templates in the Study of Complex Oligosaccharide-Receptor Interactions
Carbohydrate binding proteins are involved in myriad biological functions including communication and adhesion between cells, adhesion of bacteria or viruses, activation of the innate immune system, leukocyte rolling, hepatic clearing of aged serum proteins, and sorting of newly synthesized glycoproteins (Dwek 1996; Varki 1993). Based on their mode of binding they have been divided into three major groups. The E-, L-, and P-selectins and the galectins are of the calcium-dependent C-type lectins, which bind their ligand mainly through coordination of two vicinal hydroxy groups of a single sugar moiety to a bound calcium ion in the carbohydrate recognition domain (CRD), and the surrounding sugars of the oligosaccharide ligand add to the binding specificity through relatively weak additional interactions. Due to the nature of this interaction the specificity of selectin binding is quite broad (Kretzsch-mar et al. 1997). However, the high in vivo activity observed with selectin binding has yet to be explained.
KeywordsCarbohydrate Ketone Disulfide Galactose Sorting
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- Christensen MK, Meldal M, Bock K, Cordes H, Mouritsen S, Eisner H (1994) Synthesis of glycosylated peptide templates containing 6’-0- phosphory-lated mannose disaccharides and their binding to the cation-independent mannose-6-phosphate receptor. J Chem Soc Perkin Trans 1:1299–1310CrossRefGoogle Scholar
- Lee YC (1989) Binding modes of mammalian hepatic Gal/GalNAc receptors. In: Bock G, Harnett S (eds) Carbohydrate recognition in cellular function. Wiley, Chichester, p 80Google Scholar
- Lin C-C, Shimazaki M, Heck M-P, Aoki S, Wang R, Kimura T, Ritzen H, Takayama S, Wu S-H, Weitz-Schmidt G, Wong C-H (1996b) Synthesis of sialyl Lewis X mimetics and related structures using the glycosyl phosphite methodology and evaluation of E-selectin inhibition. J Am Chem Soc 118:6826–6840CrossRefGoogle Scholar
- Meldal M, Auzanneau F-I, Hindsgaul O, Palcic MM (1994a) A PEGA resin for use in solid phase chemical/enzymatic synthesis of glycopeptides. J Chem Soc Chem Commun 1849–1850Google Scholar
- Meldal M, Christiansen-Brams I, Christensen MK, Mouritsen S, Bock K (1994b) Synthesis and biological application of glycosylated peptide templates. In: Bock K, Clausen H (eds) Complex carbohydrates in drug research: structural and functional aspects. Copenhagen, Munksgaard, p 153Google Scholar
- St Hilaire PM, Lowary TL, Meldal M, Bock K (1998) Oligosaccharide mimet-ics obtained by novel, rapid screening of carboxylic acid encoded glycopep-tide libraries. J Am Chem Soc (submitted)Google Scholar
- Vagner J, Barany G, Lam KS, Vágner J, Barany G, Lam KS, Krechnak V, Sepetov NF, Ostrem JA, Strop P, Lebl M (1996) Enzyme-mediated spatial segregation on individual polymeric support beads: application to generation and screening of encoded combinatorial libraries. Proc Natl Acad Sci USA 93:8194–8199PubMedCrossRefGoogle Scholar