posted on 2017-11-01, 17:42authored byWalter
T. Liau, Andrea M. Kasko
Chitosan, a cationic
polysaccharide derived from one of the most
abundant natural polymers, chitin, has been investigated extensively
for its antimicrobial properties. However, it suffers from the inherent
drawbacks of natural products such as batch-to-batch variability,
limited supply, contamination, and potential adverse reaction. Additionally,
its solubility depends on the degree of deacetylation and pH, as it
is only soluble under acidic conditions. As an alternative to chitosan,
we synthesized the protected cationic glycomimetic monomer methyl N-Fmoc-6-acryloyl-β-d-glucosaminoside from
glucosamine. This monomer retains structural features critical to
recapitulating the properties of the chitosan repeat unit, namely,
the pKa of the protonated amine. We optimized
the free radical polymerization of methyl N-Fmoc-6-acryloyl-β-d-glucosaminoside and fractionated the resultant poly(methyl N-Fmoc-6-acryloyl-β-d-glucosaminoside) to
obtain a range of molecular weights. Following Fmoc deprotection,
the cationic glycopolymers retained 95% of their expected amine content
by mass and exhibited a pKa of 6.61. Poly(methyl
6-acryloyl-β-d-glucosaminoside) mimicked the molecular
weight-dependent bacterial inhibitory property of chitosan in acidic
solutions. Importantly, poly(methyl 6-acryloyl-β-d-glucosaminoside)
remained soluble at elevated pH (conditions under which chitosan is
insoluble) and maintained its antibacterial activity. Mammalian cell
viability in the presence of poly(methyl 6-acryloyl-β-d-glucosaminoside) at acidic pH is good, although somewhat lower than
viability in the presence of chitosan. No cytotoxic effect was observed
at neutral pH. These results demonstrate that poly(methyl 6-acryloyl-β-d-glucosaminoside) is not only a suitable biomimetic for chitosan,
but that it can be utilized as an antibacterial agent in a broader
range of biologically relevant pHs.