DNA glycoclusters and DNA-based carbohydrate microarrays: From design to applications

Abstract

International audienceOur goal was to design carbohydrate mimetics capable of preventing cell adhesion of pathogens by targeting lectins. The original synthesis of these mimetics combines the automated chemistry of DNA and ''click'' chemistry. From simple building blocks (i.e. phosphoramidites, solid supports and carbohydrates such as alkyne or azide derivatives), a ''Lego'' approach provides complex and varied decoys exhibiting various topologies and number of carbohydrate residues. The resulting glycomimetics tagged with a specific DNA sequence are efficiently immobilized on a DNA microarray by double strand formation. This glycoarray allows the study of the interactions between carbohydrate mimics and lectins using a minute amount of material. This micro system using DNA arrays is much more effective than conventional carbohydrate microarrays. The studies allowed the identification of the important structural parameters for a customized construction of high-affinity carbohydrate mimics

Toward the Rational Design of Galactosylated Glycoclusters That Target Pseudomonas aeruginosa Lectin A (LecA): Influence of Linker Arms That Lead to Low‐Nanomolar Multivalent Ligands

“…[33][34][35][36][37] Oligonucleotide chemistry with the powerful phosphoramidite coupling offers ag eneral and accessiblep latform for the designo fm ultivalent glycoclusters because valency can be easily modulated as well as the overall geometry of the macromolecule with optimalw ater solubility thanks to the phosphodiester groups. [14,[38][39][40][41][42][43][44] In this context, at etravalent mannopyranoside core platform was also introduced and provided glycoclustersofh igh affinity toward LecA as antibacterial candidates. [14,43,45,46] The typeo flinker used to connectt he carbohydratet ot he core also greatly affects the binding properties towardl ectins.…”

Synthesis of Azide-Modified Chondroitin Sulfate Precursors: Substrates for “Click”- Conjugation with Fluorescent Labels and Oligonucleotides

“…DNA-directed immobilization (DDI) of carbohydrates may be used to provide high throughput tools to study protein carbohydrate interactions on a DNA-based micro array. 42 The carbohydrates are usually conjugated to the 5′ end of appropriate DNA sequences and immobilized then via hybridization with the complementary strands at a specific location of the array. 42 For the preparation of the carbohydrate-oligonucleotide conjugates, a straightforward and high yielding procedure is needed.…”

Multivalent glycan arrays

“…The rigidity of the double strand nucleic acid with well-dened nucleotide spacing permits to adjust the ligand presentation on this supramolecular scaffold. [150][151][152] Similarly, peptide nucleic acids (PNAs) have been used to tag glycans and evaluate their multivalent interactions with lectins. From an assembly stand-point, stable PNA-DNA duplexes can be achieved with shorter sequences than the corresponding DNA homoduplexes (10-14-mer PNA typically provides sufficient duplex stability).…”