Chemistry Reference
In-Depth Information
surprising that several groups have focused on the postfunctionalization of alkyne-
[128-130] or azide- [131] functional oligo- and polypeptides by click glycoconju-
gation as a way to test the consequences of structural variations in lectin-binding
properties. Particularly interesting is the possibility to implement cooperative inter-
actions involving the polypeptide backbone and the appended carbohydrate ligands.
For instance, Kiic and coworkers inserted propargylglycine residues in polypeptide
sequences having affinity for the B
5
subunit of cholera toxin that were further mod-
ified with azido-functionalized galactopyranosides via CuAAC [132]. The results
evidenced the importance of saccharide spacing, polypeptide chain extension, sac-
charide linker conformation, and the placement of charges on the polypeptide back-
bone on the inhibitory potencies of glycopeptide-based multivalent inhibitors toward
this toxin.
The involvement of electrostatic interactions is particularly important for DNA
complexation. Installation of bio-recognizable carbohydrates on cationic polymers
offers a possibility to target nucleic acid material to specific cells through the forma-
tion of glycopolymer:DNA:lectin ternary complexes that can mediate cell internaliza-
tion. Reineke and coworkers have designed polyamidoamine polycationic scaffolds
bearing a controlled number of clickable alkyne sites by reaction of substituted
malondichloride derivatives (
89
,
90
), with partially Boc-protected pentaethylenehex-
amine (
91
). Click conjugation with peracetylated azidoalkyl
-D-galactopyranosides
(
92
) and final deprotection afforded polycationic glycopolymers (
93
) that efficiently
compacted plasmid DNA (pDNA) into transfectious nanoparticles that were specif-
ically recognized by the asialoprotein receptor at the cell surface of hepatocytes
(Scheme 6.16) [133].
6.5 CLICK HYBRID GLYCOMATERIALS
The term hybrid materials here refers to chimerical composites that include two
constituents amalgamated on the molecular scale, where one of these moieties is
commonly inorganic and the other organic in nature. Hybrid materials represent one
of the most fascinating progresses in materials sciences with applications in many
branches, from biomedicine to organic solar cells [134]. Carbohydrates, as a prime
class of biomolecules, have not remained apart from these developments. Taking
into account the multifunctional and, quite often, fragile nature of saccharides, a
major prerequisite for the preparation of hybrid glycomaterials is to proceed through
bioorthogonal reaction conditions that combine mildness and efficiency. The CuAAC
reaction perfectly meets these requirements, which has translated into an enormous
impact in the field.
Among hybrid glycomaterials, glyconanomaterials, carbohydrate-decorated nano-
metric scale materials, are creating a high expectation in glycobiology. The merging
between the glycosciences and the nanosciences (
glyconanotechnology
) provides new
devices for more accurate fundamental studies and opens new and exciting opportu-
nities in the biomedical field. Glyconanomaterials are creating a high expectation in
areas such as diagnostics, therapy, drug-delivery-controlled drug release and, tissue
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