Tunable synthetic polymeric scavengers for toxic xenobiotics
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Faculty of Chemistry, M. V. Lomonosov Moscow State University, Moscow, Russia
Publication date: 2022-05-27
Public Health Toxicol 2022;2(Supplement 2):A8
Toxins present danger to human health. This work is focusing on ochratoxin A (OTA). It exhibits mutagenic, carcinogenic, neurotoxic properties which are harmful to human health. OTA is produced by some species of Aspergillus and Penicillium and exposure can occur by consumption of contaminated food products such as grain, pork, coffee and other food products.
The selective binding of toxic compounds finds its potential application both in sensor construction for analytical purposes and in treating patients recently exposed to harmful substances. Chemically designed macromolecules may demonstrate enhanced affinity for target compounds. Main goal of this work was to synthesize polymeric scavenger, that would be able to bind OTA. A polymer bearing azide groups was synthesized and was further introduced into Cu(I)-catalyzed azide-alkyne cycloaddition (CuAAC) with different alkynes. The ability of alkyne-modified polymers to bind OTA was estimated using plasmon resonance spectroscopy technique. OTA was immobilized on the gold surface of the chip, and equilibrium dissociation constant (KD) was measured.
For the proof of the concept, the side groups of the block copolymer PEG114-pGlu10 were modified using 3-azido-1-propylamine via EDC/NHS reaction. The product was further introduced in CuAAC with first alkyne 1-ethyl-4-ethynylbenzene. The resulted polymer exhibits moderate affinity to OTA (KD = 0.5 ± 0.1 mM). HPMA-based polymer was synthesized for future use as parent compound. Six different methods of N-(2-hydroxypropyl)methacrylamide (HPMA) synthesis were used to obtain the higher yield [76%, 1H-NMR (300MHz, D2O) δ (ppm): 1.05 (d, 3H, CH-CH3), 1.79 (s, 3H, CH3-C), 3.10 (m, 1H, CH2-NH), 3.85 (m, 2H, CH-CH3), 5.31 (s, 1H, CH2=C), and 5.56 (s, 1H, CH2=C)].
This work was supported in part by Russian Science Foundation (Grant Number: 20-63-46029), Lomonosov MSU Reg. Theme 121041500039-8 and MSU Program of Development.