Coassembly of amphiphilic peptide EAK16-II with histidinylated analogues and implications for functionalization of 尾-sheet fibrils in聽vivo

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• 作者：Yi Wen^a ; Shana L. Roudebush^a ; Gavin A. Buckholtz^b ; Thomas R. Goehring^a ; Nick Giannoukakis^c ; ^d ; Ellen S. Gawalt^b ; ^e ; Wilson S. Meng^a ; ^{meng@duq.edu" class="auth_mail}
• 关键词：EAK16 ; Cross-尾 fibrils ; Self-assembly ; Amphiphilic peptides ; Protein formulation
• 刊名：Biomaterials
• 出版年：June, 2014
• 年：2014
• 卷：35
• 期：19
• 页码：5196-5205
• 全文大小：1412 K

文摘

EAK16-II (AEAEAKAKAEAEAKAK) is one of the first building blocks of environmentally responsive materials. This self-assembling peptide undergoes solution-to-gel transition when transferred from a low to high ionic strength environment. Previously we have demonstrated the histidinylated analogue聽EAKIIH6 (AEAEAKAKAEAEAKAKHHHHHH) coassembles with the parent peptide to render His-tags as a functionalization mechanism in聽vitro and in聽vivo. The present study aimed to understand the pathways by which the analogue聽coassembles with EAK16-II. The results presented herein suggested two competing but not mutually exclusive events in the coassembly. Atomic force microscopic and gel electrophoretic data showed that EAKIIH6 self-sorted to high molecular weight species without EAK16-II. Self-sorting of EAKIIH6 was inhibited by the parent peptide in a concentration dependent manner. Injecting mixtures containing EAKIIH6 subcutaneously rendered His-tags detectable in live mice for at least 312聽h, despite diluting the histidinylated analogue聽by 10-50 folds compared to a previous formulation. The study provided a formulation by which in聽vivo display of His-tags was attained without excess amphiphilic peptides. By increasing coassembling efficiency, the likelihood of generating immunogenic aggregates outside the main fibrils could be minimized. These findings provide insights for rational functionalization of in situ self-gelling materials.