A convenient and efficient approach
for the surface modification
of antifouling materials is highly desirable in numerous applications
like affinity-based biosensors. Herein, we fabricated a hybrid antifouling
coating on Au surfaces, with thiolated hyaluronic acid (HA) being
chemically adsorbed to Au surfaces by the “graft to”
approach, followed by a self-assembly of a smaller zwitterionic peptide
named p-EK to obtain HA/p-EK-modified surfaces. The real-time sensorgrams
of surface plasmon resonance biosensor manifested the successful modification
of HA and p-EK on Au surfaces, indicating that there were some bare
Au substrates on the HA-modified surfaces for peptide binding.
The obtained HA/p-EK surfaces exhibited high hydrophilicity with a
water contact angle of 9°. Quartz crystal microbalance and surface
plasmon resonance experiments verified that further grafting the zwitterionic
p-EK peptide on HA-modified surfaces could enhance the antifouling
performance by one time. The improved protein resistance could be
mainly contributed by the modification of the zwitterionic peptide
that shields the exposed Au substrates from interacting with protein
foulings. This strategy by grafting a smaller zwitterionic peptide
might provide a novel way to achieve an enhanced protein-resistant
performance of the macromolecular coating obtained by the “graft
to” surface modification approach.
Anthrax toxin is the major virulence factor produced by Bacillus anthracis. The toxin consists of three protein subunits: protective antigen (PA), lethal factor, and edema factor. Inhibition of PA binding to its receptors, tumor endothelium marker-8 (TEM8) and capillary morphogenesis protein-2 (CMG2) can effectively block anthrax intoxication, which is particularly valuable when the toxin has already been overproduced at the late stage of anthrax infection, thus rendering antibiotics ineffectual. Receptor-like agonists, such as the mammalian cell-expressed von Willebrand factor type A (vWA) domain of CMG2 (sCMG2), have demonstrated potency against the anthrax toxin. However, the soluble vWA domain of TEM8 (sTEM8) was ruled out as an anthrax toxin inhibitor candidate due to its inferior affinity to PA. In the present study, we report that L56A, a PA-binding-affinity-elevated mutant of sTEM8, could inhibit anthrax intoxication as effectively as sCMG2 in Fisher 344 rats. Additionally, pharmacokinetics showed that L56A and sTEM8 exhibit advantages over sCMG2 with better lung-targeting and longer plasma retention time, which may contribute to their enhanced protective ability in vivo. Our results suggest that receptor decoys based on TEM8 are promising anthrax toxin inhibitors and, together with the pharmacokinetic studies in this report, may contribute to the development of novel anthrax drugs.
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