Department of Organic Chemistry, School of Chemistry, Faculty of Exact Sciences, Tel-Aviv University , Tel-Aviv 6997801, Israel.
Tel-Aviv University Center for Nanoscience and Nanotechnology, Tel-Aviv University , Tel-Aviv 6997801, Israel.
J Am Chem Soc. 2017 Jan 18;139(2):803-810. doi: 10.1021/jacs.6b10624. Epub 2017 Jan 4.
Studying the enzymatic degradation of synthetic polymers is crucial for the design of suitable materials for biomedical applications ranging from advanced drug delivery systems to tissue engineering. One of the key parameters that governs enzymatic activity is the limited accessibility of the enzyme to its substrates that may be collapsed inside hydrophobic domains. PEG-dendron amphiphiles can serve as powerful tools for the study of enzymatic hydrolysis of polymeric amphiphiles due to the monodispersity and symmetry of the hydrophobic dendritic block, which significantly simplifies kinetic analyses. Using these hybrids, we demonstrate how precise, minor changes in the hydrophobic block are manifested into tremendous changes in the stability of the assembled micelles toward enzymatic degradation. The obtained results emphasize the extreme sensitivity of self-assembly and its great importance in regulating the accessibility of enzymes to their substrates. Furthermore, the demonstration that the structural differences between readily degradable and undegradable micelles are rather minor, points to the critical roles that self-assembly and polydispersity play in designing biodegradable materials.
研究合成聚合物的酶降解对于设计适用于生物医学应用的材料至关重要，这些应用范围从先进的药物输送系统到组织工程。影响酶活性的一个关键参数是酶对其底物的有限可及性，这些底物可能在疏水区内塌陷。PEG-树状大分子两亲物由于疏水性树枝状块的单分散性和对称性，可以作为研究聚合物两亲物酶水解的有力工具，这大大简化了动力学分析。使用这些杂化物，我们展示了疏水性块的微小精确变化如何表现为组装胶束对酶降解稳定性的巨大变化。所得结果强调了自组装的极端敏感性及其在调节酶对其底物的可及性方面的重要性。此外，证明可降解和不可降解胶束之间的结构差异相当小，这表明自组装和多分散性在设计可生物降解材料方面起着关键作用。
