Defining HIV envelope glycoprotein interactions with host factors or binding partners advances our understanding of the infectious process and provides a basis for the design of vaccines and agents that interfere with HIV entry. Here we employ carbohydrate and glycoprotein microarrays to analyze glycan-dependent gp120-protein interactions. In concert with new linking chemistries and synthetic methods, the carbohydrate arrays combine the advantages of microarray technology with the flexibility and precision afforded by organic synthesis. With these microarrays, we individually and competitively determined the binding profiles of five gp120 binding proteins, established the carbohydrate structural requirements for these interactions, and identified a potential strategy for HIV vaccine development.
The emerging field of glycomics has been challenged by difficulties associated with studying complex carbohydrates and glycoconjugates. Advances in the development of synthetic tools for glycobiology are poised to overcome some of these challenges and accelerate progress towards our understanding of the roles of carbohydrates in biology. Carbohydrate microarrays, fluorescent neoglycoconjugate probes, and aminoglycoside antibiotic microarrays are among the many new tools becoming available to glycobiologists.
On the spot: Carbohydrate microarrays, in concert with surface plasmon resonance, are valuable tools in the rapid identification of carbohydrate–protein interactions, like those between high‐mannose oligosaccharides and cyanovirin‐N (see picture). By utilizing chemical methods amenable to current high‐throughput screening technologies, high‐density carbohydrate microarrays can be prepared and screened by using conventional and widely accessible DNA microarray screening instrumentation.
The unique therapeutic value of dendritic cells (DCs) for the treatment of allergy, autoimmunity and transplant rejection is predicated upon our ability to selectively deliver antigens, drugs or nucleic acids to DCs in vivo. Here we describe a method for delivering whole protein antigens to DCs based on carbohydrate-mediated targeting of DC-expressed lectins. A series of synthetic carbohydrates was chemically-coupled to a model antigen, ovalbumin (OVA), and each conjugate was evaluated for its ability to increase the efficiency of antigen presentation by murine DCs to OVA-specific T cells (CD4 + and CD8 + ). In vitro data are presented that demonstrate that carbohydrate modification of OVA leads to a 50-fold enhancement of presentation of antigenic peptide to CD4 + T cells. A tenfold enhancement is observed for CD8 + T cells; this indicates that the targeted lectin(s) can mediate crosspresentation of antigens on MHC class I. Our data indicate that the observed enhancements in antigen presentation are unique to OVA that is conjugated to complex oligosaccharides, such as a highmannose nonasaccharide, but not to monosaccharides. Taken together, our data suggest that a DC targeting strategy that is based upon carbohydrate-lectin interactions is a promising approach for enhancing antigen presentation via class I and class II molecules.
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