Syntheses of 6-sulfo sialyl Lewis X glycans corresponding to the L-selectin ligand "sulfoadhesin"

[structure: see text] Divergent syntheses of sulfated sialyl Lewis X oligosaccharides corresponding to the core 1 and core 6 branches of the L-selectin ligand are reported. These synthetic targets incorporate a selectively protected serine residue at the reducing terminus, providing a functional handle for further conjugation.     

A strain-promoted [3 + 2] azide-alkyne cycloaddition for covalent modification of biomolecules in living systems

Selective chemical reactions that are orthogonal to the diverse functionality of biological systems have become important tools in the field of chemical biology. Two notable examples are the Staudinger ligation of azides and phosphines and the Cu(I)-catalyzed [3 + 2] cycloaddition of azides and alkynes ("click chemistry"). The Staudinger ligation has sufficient biocompatibility for performance in living animals but suffers from phosphine oxidation and synthetic challenges. Click chemistry obviates the requirement of phosphines, but the Cu(I) catalyst is toxic to cells, thereby precluding in vivo applications. Here we present a strain-promoted [3 + 2] cycloaddition between cyclooctynes and azides that proceeds under physiological conditions without the need for a catalyst. The utility of the reaction was demonstrated by selective modification of biomolecules in vitro and on living cells, with no apparent toxicity.     

A "traceless" Staudinger ligation for the chemoselective synthesis of amide bonds

[reaction: see text] Here we report a novel modification of our previously reported "Staudinger ligation" that generates an amide bond from an azide and a specifically functionalized phosphine. This method for the selective formation of an amide bond, which does not require the orthogonal protection of distal functional groups, should find general utility in synthetic and biological chemistry.     

Chemical synthesis of lymphotactin: a glycosylated chemokine with a C-terminal mucin-like domain

The synthesis of a 93-residue chemokine, lymphotactin, containing eight sites of O-linked glycosylation, was achieved using the technique of native chemical ligation. A single GalNAc residue was incorporated at each glycosylation site using standard Fmoc-chemistry to achieve the first total synthesis of a mucin-type glycoprotein. Using this approach quantities of homogeneous material were obtained for structural and functional analysis.     

Chemoselective ligation applied to the synthesis of a biantennary N-linked glycoform of CD52

We report here a strategy for the synthesis of N-linked glycopeptide analogues that replace the glycosidic linkages extending from the core pentasaccharide with thioethers amenable to construction by chemoselective ligation. The key building block, a pentasaccharide-Asn analogue containing two thiol residues, was incorporated into CD52 by 9-fluorenylmethoxycarbonyl (Fmoc)-based solid-phase peptide synthesis. An undecasaccharide mimetic was then readily generated by alkylation of this glycopeptide with an N-bromoacetamido trisaccharide. The rapid assembly of a complex type N-linked glycopeptide mimetic was accomplished using this technique.     

An inhibitor of the human UDP-GlcNAc 4-epimerase identified from a uridine-based library: a strategy to inhibit O-linked glycosylation

The biological study of O-linked glycosylation is particularly problematic, as chemical tools to control this modification are lacking. An inhibitor of the UDP-GlcNAc 4-epimerase that synthesizes UDP-GalNAc, the donor initiating O-linked glycosylation, would be a powerful reagent for reversibly inhibiting O-linked glycosylation. We synthesized a 1338 member library of uridine analogs directed to the epimerase by virtue of substrate mimicry. Screening of the library identified an inhibitor with a K(i) value of 11 microM. Tests against related enzymes confirmed the compound's specificity for the UDP-GlcNAc 4-epimerase. Inhibitors of a key step of O-linked glycan biosynthesis can be discovered from a directed library screen. Progeny thereof may be powerful tools for controlling O-linked glycosylation in cells.     

Convergence of the Graph Allen–Cahn Scheme

Journal of Statistical Physics - The graph Laplacian and the graph cut problem are closely related to Markov random fields, and have many applications in clustering and image segmentation. The...     

Geographical influences of an emerging network of gang rivalries

We propose an agent-based model to simulate the creation of street gang rivalries. The movement dynamics of agents are coupled to an evolving network of gang rivalries, which is determined by previous interactions among agents in the system. Basic gang data, geographic information, and behavioral dynamics suggested by the criminology literature are integrated into the model. The major highways, rivers, and the locations of gangs’ centers of activity influence the agents’ motion. We use a policing division of the Los Angeles Police Department as a case study to test our model. We apply common metrics from graph theory to analyze our model, comparing networks produced by our simulations and an instance of a Geographical Threshold Graph to the existing network from the criminology literature.