Abstracts Book - IMRC 2018

• SB1-O026 Invited Talk
POLY(METHYL 6-ACRYLOYL-β-D-GLUCOSAMINOSIDE) AS A
CATIONIC GLYCOMIMETIC OF CHITOSAN
Andrea M. Kasko 1
1 University of California, Los Angeles, Bioengineering, United States.
Chitosan, a cationic polysaccharide derived one of the most abundant natural
polymers, chitin, has been investigated extensively for its antimicrobial properties.
However, it suffers the inherent drawbacks of natural products such as batch-tobatch
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-Dglucosaminoside
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 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-Dglucosaminoside)
mimicked the molecular weight-dependent bacterial inhibitory
property of chitosan in acidic solutions. Importantly, poly(methyl 6-acryloyl-β-Dglucosaminoside)
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.
Acknowledgment: This work was supported by the National Science
Foundation under CHE-1112490 as well as an equipment grant CHE-1048804.
W.T.L. was supported by a fellowship the NSF IGERT: Materials Creation
Training Program, DGE-0654431.
Keywords: glycomimetic, chitosan, cationic polymer
Presenting authors email: akasko@ucla.edu