Department of Bioengineering and ‡Department of Chemistry and Biochemistry, University of California , Los Angeles, California 90095, United States.
Biomacromolecules. 2013 Oct 14;14(10):3610-4. doi: 10.1021/bm400971p. Epub 2013 Sep 9.
We have developed a facile, scalable method for preparation of enzyme-responsive copolypeptide vesicles that requires no protecting groups or expensive components. We designed amphiphilic copolypeptides containing segments of water-soluble methionine sulfoxide, M(O), residues that were prepared by synthesis of a fully hydrophobic precursor diblock copolypeptide, poly(l-methionine)65-b-poly(L-leucine0.5-stat-L-phenylalanine0.5)20, M65(L0.5/F0.5)20, followed by its direct oxidation in water to give the amphiphilic M(O) derivative, M(O)65(L0.5/F0.5)20. Assembly of M(O)65(L0.5/F0.5)20 in water gave vesicles with average diameters of a few micrometers that could then be extruded to nanoscale diameters. The M(O) segments in the vesicles were found to be substrates for reductase enzymes, which regenerated hydrophobic M segments and resulted in a change in supramolecular morphology that caused vesicle disruption and release of cargos.
我们开发了一种简便、可扩展的方法来制备酶响应性共聚多肽囊泡，该方法不需要保护基团或昂贵的成分。我们设计了含有水溶性蛋氨酸亚砜（M(O)）片段的两亲性共聚多肽，这些片段是通过合成完全疏水的前体二嵌段共聚多肽聚（L-蛋氨酸）65-b-聚（L-亮氨酸 0.5-Stat-L-苯丙氨酸 0.5）20 来制备的，然后在水中直接氧化得到两亲性 M(O)衍生物 M(O)65(L0.5/F0.5)20。M(O)65(L0.5/F0.5)20 在水中组装成几微米大小的囊泡，然后可以挤出到纳米尺寸。囊泡中的 M(O) 片段被还原酶酶的底物，这些酶再生疏水性 M 片段，导致超分子形态发生变化，导致囊泡破裂和货物释放。
