Effects of Side Group Functionality and Molecular Weight on the Activity of Synthetic Antimicrobial Polypeptides
Effects of Side Group Functionality and Molecular Weight on the Activity of Synthetic Antimicrobial Polypeptides
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DOI：
10.1021/bm2000583
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发表时间：
2011-05-01
影响因子：
6.2
通讯作者：
Hammond, Paula T.
中科院分区：
文献类型：
--
作者：
Engler, Amanda C.;Shukla, Anita;Hammond, Paula T.
耐药性细菌的迅速出现沿着生物膜治疗的难度增加，已经引起了对开发新类别的抗微生物治疗剂的迫切需要。我们已经开发了一个库的抗菌肽，制备的γ-炔丙基-L-谷氨酸N-羧酸酐的开环聚合和炔-叠氮环加成点击反应，这模拟了天然存在的抗菌肽（AmPs）的有利特性。已知AmPs不会引起耐药性以及防止细菌附着在表面上。与天然存在的抗微生物肽所需的传统梅里菲尔德合成肽方法相比，本文开发的抗微生物多肽的合成的容易性和规模得到显著改善，并且避免了生物合成途径的独特挑战。多肽的长度范围为30至140个重复单元，并且可以具有不同的侧基官能度，包括具有1至12个碳长的烃侧链的伯胺、仲胺、叔胺和季胺。总之，我们发现这些多肽对革兰氏阳性和革兰氏阴性细菌，即S. aureus和E.大肠杆菌，而具有非常低的溶血活性。许多多肽也可用作表面涂层以防止细菌附着。在这项工作中开发的多肽库解决了对用于药物递送和医疗器械涂层的有效生物相容性治疗剂的需求。
The rapid emergence of antibiotic-resistant bacteria along with increasing difficulty in biofilm treatment has caused an immediate need for the development of new classes of antimicrobial therapeutics. We have developed a library of antimicrobial polypeptides, prepared by the ring-opening polymerization of gamma-propargyl-L-glutamate N-carboxyanhydride and the alkyne-azide cycloaddition click reaction, which mimic the favorable characteristics of naturally occurring antimicrobial peptides (AmPs). AmPs are known not to cause drug resistance as well as prevent bacteria attachment on surfaces. The ease and scale of synthesis of the antimicrobial polypeptides developed here are significantly improved over the traditional Merrifield synthetic peptide approaches needed for naturally occurring antimicrobial peptides and avoids the unique challenges of biosynthetic pathways. The polypeptides range in length from 30 to 140 repeat units and can have varied side group functionality, including primary, secondary, tertiary, and quaternary amines with hydrocarbon side chains ranging from 1 to 12 carbons long. Overall, we find these polypeptides to exhibit broad-spectrum activity against both Gram positive and Gram negative bacteria, namely, S. aureus and E. coli, while having very low hemolytic activity. Many of the polypeptides can also be used as surface coatings to prevent bacterial attachment. The polypeptide library developed in this work addresses the need for effective biocompatible therapeutics for drug delivery and medical device coatings.