Acetylation of alcohols, phenols, thiols and amines catalysed by H-beta zeolite

892-894The acetylation of several alcohols, phenols, thiols and amines was effected at room temperature: in excellent yields using H-beta zeolite as catalyst and acetic anhydride as acetylating agent under mostly solvent-free conditions

Clickable Glycopeptoids for Synthesis of Glycopeptide Mimic

Structurally diverse novel glycopeptoids were synthesized which can be attached to biologically important peptides by <i>click reaction</i> to improve their potential to be used in medicinal chemistry. Triazole-linked αβ-hydrid glycopeptoids were synthesized that mimic the conserved linkage region of N-linked glycoproteins in eukaryotes. The amide bonds were replaced with triazole rings, and αβ-hybrid peptoids were introduced as the backbone modification in peptido­mimetics. In addition to their facile synthesis, these modifications have the possibility of introducing otherwise impossible conformations in the peptide backbone

Synthesis and Assessment of Glycosaminoglycan Priming Activity of Cluster-xylosides for Potential Use as Proteoglycan Mimetics

One of the distinct structural features of many proteoglycans (PGs) is the presence of two or more glycosaminoglycan (GAG) side chains covalently linked to a core protein. Previous studies have shown that the synergistic biological activity of multiple GAG chains, as found in the majority of PGs, cannot be accomplished by the sum of the activities of individual GAG chains. To delineate the biological significance of GAG valency, a number of cluster-xylosides carrying two, three, or four xylose residues on the same scaffold were synthesized using click chemistry. Assessment of cluster-xylosides for their GAG chain priming activity in a cellular system revealed that these cluster-xylosides prime multiple GAG chains per scaffold. Multivalent GAG chains, produced by cluster-xylosides, can better mimic PGs as they carry two or more GAG chains attached to a core protein and therefore can be used as molecular probes to examine the biological significance of GAG multivalency in model organisms

Dimerized Glycosaminoglycan Chains Increase FGF Signaling during Zebrafish Development

Proteoglycans (PGs) modulate numerous signaling pathways during development through binding of their glycosaminoglycan (GAG) side chains to various signaling molecules, including fibroblast growth factors (FGFs). A majority of PGs possess two or more GAG side chains, suggesting that GAG multivalency is imperative for biological functions <i>in vivo</i>. However, only a few studies have examined the biological significance of GAG multivalency. In this report, we utilized a library of bis- and tris-xylosides that produce two and three GAG chains on the same scaffold, respectively, thus mimicking PGs, to examine the importance of GAG valency and chain type in regulating FGF/FGFR interactions <i>in vivo</i> in zebrafish. A number of bis- and tris-xylosides, but not mono-xylosides, caused an elongation phenotype upon their injection into embryos. <i>In situ</i> hybridization showed that elongated embryos have elevated expression of the FGF target gene <i>mkp3</i> but unchanged expression of reporters for other pathways, indicating that FGF/FGFR signaling was specifically hyperactivated. In support of this observation, elongation can be reversed by the tyrosine kinase inhibitor SU5402, mRNA for the FGFR antagonist <i>sprouty4</i>, or FGF8 morpholino. Endogenous GAGs seem to be unaffected after xyloside treatment, suggesting that this is a gain-of-function phenotype. Furthermore, expression of a multivalent but not a monovalent GAG containing syndecan-1 proteoglycan recapitulates the elongation phenotype observed with the bivalent xylosides. On the basis of these <i>in vivo</i> findings, we propose a new model for GAG/FGF/FGFR interactions in which dimerized GAG chains can activate FGF-mediated signal transduction pathways