Department of Chemistry and Chemical Technology , Al-Farabi Kazakh National University , 71 Al-Farabi Avenue , Almaty 050040 , Republic of Kazakhstan.
Biomacromolecules. 2019 Jun 10;20(6):2392-2405. doi: 10.1021/acs.biomac.9b00379. Epub 2019 May 22.
When grown from the surface of proteins, negatively charged polymers cause irreversible inactivation, thereby limiting the breadth of the synthetic space that negatively charged protein-polymer conjugates can be applied to. More broadly speaking, independent of polymer and synthetic approach, almost all protein-polymer conjugates are less active than their precursors. After more than a decade without major advances in understanding why the attachment of some polymers so sharply deactivates enzymes, we focused our attention on a technique to protect enzymes from the growth of a deactivating polymer by restoring the charge at the protein surface during polymer attachment. We synthesized an amino-reactive positively charged atom transfer radical polymerization initiator that inserted a permanent positive charge at the site of bio-macroinitiator attachment. Preserving the surface charge through attachment of the permanent positively charged initiator led to the first observation of activity of enzymes that were coupled to negatively charged homopolymers.
当从蛋白质表面生长时，带负电荷的聚合物会导致不可逆失活，从而限制了可应用于带负电荷的蛋白质-聚合物缀合物的合成空间的广度。更广泛地说，与聚合物和合成方法无关，几乎所有的蛋白质-聚合物缀合物的活性都低于其前体。在十多年来对为什么附着某些聚合物会如此急剧地使酶失活的理解没有重大进展之后，我们将注意力集中在一种通过在聚合物附着过程中恢复蛋白质表面的电荷来保护酶免受失活聚合物生长影响的技术上。我们合成了一种反应性氨基的正碳离子原子转移自由基聚合引发剂，它在生物大分子引发剂附着的部位插入了一个永久的正电荷。通过附着永久正电荷引发剂来保持表面电荷，导致首次观察到与带负电荷的均聚物偶联的酶的活性。
