A Visualizable Chain‐Terminating Inhibitor of Glycosaminoglycan Biosynthesis in Developing Zebrafish

Heparan sulfate (HS) and chondroitin sulfate (CS) glycosaminoglycans (GAG) are proteoglycan‐associated polysaccharides with essential functions in animals. They have been studied extensively by genetic manipulation of biosynthetic enzymes, but chemical tools for probing GAG function are limited. HS and CS possess a conserved xylose residue that links the polysaccharide chain to a protein backbone. Here we report that, in zebrafish embryos, the peptide‐proximal xylose residue can be metabolically replaced with a chain‐terminating 4‐azido‐4‐deoxyxylose (4‐XylAz) residue by administration of UDP‐4‐azido‐4‐deoxyxylose (UDP‐4‐XylAz). UDP‐4‐XylAz disrupted both HS and CS biosynthesis and caused developmental abnormalities reminiscent of GAG biosynthesis and laminin mutants. The azide substituent of protein‐bound 4‐XylAz allowed for rapid visualization of the organismal sites of chain termination in vivo through bioorthogonal reaction with fluorescent cyclooctyne probes. UDP‐4‐XylAz therefore complements genetic tools for studies of GAG function in zebrafish embryogenesis.     

Synthesis of 2- and 2,3-substituted pyrazolo[1,5-a]pyridines: scope and mechanistic considerations of a domino direct alkynylation and cyclization of N-iminopyridinium ylides using alkenyl bromides, alkenyl iodides, and alkynes

Direct functionalization and tandem processes have both received considerable recent interest due to their cost and time efficiency. Herein we report the synthesis of difficult to obtain 2-substituted pyrazolo[1,5-a]pyridines through a tandem palladium-catalyzed/silver-mediated elimination/direct functionalization/cyclization reaction involving N-benzoyliminopyridinium ylides. As such, these biologically important molecules are prepared in an efficient, high-yielding manner, only requiring a two-step sequence from pyridine. Aryl-substituted alkenyl bromides and iodides are effective ylide coupling partners. Mechanistic studies led to the use of terminal alkynes, which extended the scope of the reaction to include alkyl substitution on the unsaturated reactive site. The optimization, scope, and mechanistic considerations of the process are discussed.     

Effects of surface heterogeneity on flow circulation in electroosmotic flow in microchannels

The characteristics of electroosmotic flow in a cylindrical microchannel with non-uniform zeta potential distribution are investigated in this paper. Two-dimensional full Navier–Stokes equation is used to model the flow field and the pressure field. The numerical results show the distorted electroosmotic velocity profiles and various kinds of flow circulation resulting from the axial variation of the zeta potential. The influences of heterogeneous patterns of zeta potential on the velocity profile, the induced pressure distribution and the volumetric flow rate are discussed in this paper. This work shows that using either heterogeneous patterns of zeta potential or a combination of a heterogeneous zeta potential distribution and an applied pressure difference over the channel can generate local flow circulations and hence provide effective means to improve the mixing between different solutions in microchannels.