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通过硫醇-烯点击化学共价连接稳定化抗菌肽方便地制备杀菌水凝胶

Convenient Preparation of Bactericidal Hydrogels by Covalent Attachment of Stabilized Antimicrobial Peptides Using Thiol-ene Click Chemistry.

作者信息

Cleophas Rik T C, Riool Martijn, Quarles van Ufford H Linda C, Zaat Sebastian A J, Kruijtzer John A W, Liskamp Rob M J

机构信息

Department of Medicinal Chemistry and Chemical Biology, Utrecht Institute for Pharmaceutical Sciences, Faculty of Science, Utrecht University, Universiteitsweg 99, 3584 CG, 3584 CA, Utrecht, The Netherlands.

Department of Medical Microbiology, Center for Infection and Immunity Amsterdam (CINIMA), Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ Amsterdam, The Netherlands.

出版信息

ACS Macro Lett. 2014 May 20;3(5):477-480. doi: 10.1021/mz5001465. Epub 2014 May 7.

Abstract

This report describes the design and synthesis of a bactericidal poly(ethylene glycol)-based (PEG) hydrogel coating with covalently attached antimicrobial peptides (AMP) stabilized against proteolytic degradation. As such, mimics of the highly active AMP HHC10 (H-KRWWKWIRW-NH) were designed for optimal stability in human serum while retaining strong antimicrobial activity against and , the major causative agents of biomaterial associated infection. In order to investigate the selectivity of the AMPs, their hemolytic activity was determined. A N-terminal cysteine facilitated thiol-ene chemistry for a fast, single-step immobilization/photopolymerization strategy. The antimicrobial activity of the resulting thin layer hydrogel coating on a PET surface was established using the Japanese Industrial Standard (JIS) Z2801 assay, showing complete killing (>99.9%) of inocula of ATCC 49230, ATCC 35984, and ATCC 8739.

摘要

本报告描述了一种基于聚乙二醇(PEG)的杀菌水凝胶涂层的设计与合成,该涂层带有共价连接的抗菌肽(AMP),可稳定抵抗蛋白水解降解。因此,设计了高活性AMP HHC10(H-KRWWKWIRW-NH)的模拟物,以在人血清中实现最佳稳定性,同时对生物材料相关感染的主要病原体金黄色葡萄球菌和大肠杆菌保持强大的抗菌活性。为了研究AMP的选择性,测定了它们的溶血活性。N端半胱氨酸促进了硫醇-烯化学,实现了快速、一步固定/光聚合策略。使用日本工业标准(JIS)Z2801试验确定了所得PET表面薄层水凝胶涂层的抗菌活性,结果显示对金黄色葡萄球菌ATCC 49230、大肠杆菌ATCC 35984和白色念珠菌ATCC 8739的接种物有完全杀灭作用(>99.9%)。

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