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Tuning the allosteric sequestration of anticancer drugs for developing cooperative nano-antidotes. | LitMetric
A dual-cavity basket 1, holding six γ-aminobutyric acids at its termini, encapsulates variously sized aromatics 2-7, including four anthracyclines (8-11), driven by the hydrophobic effect and hydrogen bonding (HB). In particular, the formation of stable (K = 10 M) anthracycline complexes [(8-11)⊂1], assembled into nanoparticles, occurred with positive homotropic cooperativity (α = 4K/K = 1.1 ± 0.3 × 10-1.3 ± 0.7 × 10) in PBS medium. Importantly, weakening the first binding event (K, i.e. by removing HBs) turned the second one (K) more favorable. The finding is of interest for developing cooperative nano-antidotes acting as biodetoxifying agents.
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