Department of Chemistry, University of Reading, Whiteknights, Reading RG6 6AD, UK.
Langmuir. 2010 Jul 20;26(14):11624-7. doi: 10.1021/la101806z.
A micellar nanocontainer delivery and release system is designed on the basis of a peptide-polymer conjugate. The hybrid molecules self-assemble into micelles comprising a modified amyloid peptide core surrounded by a PEG corona. The modified amyloid peptide previously studied in our group forms helical ribbons based on a beta-sheet motif and contains beta-amino acids that are excluded from the beta-sheet structure, thus being potentially useful as fibrillization inhibitors. In the model peptide-PEG hybrid system studied, enzymatic degradation using alpha-chymotrypsin leads to selective cleavage close to the PEG-peptide linkage, break up of the micelles, and release of peptides in unassociated form. The release of monomeric peptide is useful because aggregation of the released peptide into beta-sheet amyloid fibrils is not observed. This concept has considerable potential in the targeted delivery of peptides for therapeutic applications.
一种胶束纳米容器递释系统是基于肽-聚合物缀合物设计的。该混合分子自组装成胶束,由修饰的淀粉样肽核心和 PEG 冠层组成。我们小组之前研究的修饰淀粉样肽基于β-折叠基序形成螺旋带,并且含有被排除在β-折叠结构之外的β-氨基酸,因此可能作为纤维化抑制剂很有用。在研究的模型肽-PEG 混合系统中,使用糜蛋白酶进行酶降解导致在靠近 PEG-肽键处的选择性切割,胶束解体,并以未缔合形式释放肽。释放单体肽是有用的,因为释放的肽聚集到β-折叠淀粉样纤维中没有观察到。这个概念在肽的靶向递释方面具有相当大的应用潜力,可用于治疗应用。