Affinity Mesh Screen Materials for Selective Extraction
and Analysis of Antibiotics Using Transmission Mode Desorption Electrospray
Ionization Mass Spectrometry
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Abstract
The extraction of active compounds
from natural sources has shown
to be an effective approach to drug discovery. However, the isolation
and identification of natural products from complex extracts can be
an arduous task. A novel approach to drug discovery is presented through
the use of polymer screens functionalized with an l-lysine-d-alanine-d-alanine (Kaa) peptide to create new affinity
capture mesh screen materials. The Kaa sequence is a well-characterized
specific binding site for antibiotics that inhibit cell wall synthesis
in Gram-positive bacteria. The detailed synthesis and characterization
of these novel screen materials are presented in this work. Polypropylene
mesh screens were first coated with a poly(acrylic acid) film by pulsed
plasma polymerization. The synthesized Kaa peptide was then covalently
attached to carboxylic acid groups through a condensation reaction.
An analysis of captured compounds was performed in a rapid fashion
with transmission-mode desorption electrospray ionization (TM-DESI)
mass spectrometry. A proof of principle was demonstrated to show the
ability of the novel affinity capture materials to select for a macrocyclic
antibiotic, vancomycin, over a negative control compound, spectinomycin.
With further development, this method may provide a rapid screening
technique for new antibacterial compounds, for example, those extracted
from natural product sources having a limited supply. Here, we show
that the screen can capture vancomycin preferentially over spectinomycin
in a spiked extract of tea leaves