Improved antimicrobial activity of h-lysozyme (107-115) by rational Ala substitution
Improved antimicrobial activity of h-lysozyme (107-115) by rational Ala substitution
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DOI：
10.1002/psc.1258
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发表时间：
2010-08-01
影响因子：
2.1
通讯作者：
Iannucci, Nancy B.
中科院分区：
文献类型：
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作者：
Gonzalez, Rodrigo;Albericio, Fernando;Iannucci, Nancy B.
在设计新的抗微生物剂中最具挑战性的目标是抗生素耐药性的发展。抗菌肽是开发新型抗感染药物的先导化合物。在这里，我们提出的顺序取代每个Ala残基存在于一个已知的抗菌活性的前导肽的特定氨基酸，合理选择，可以提高所得肽的活性。以人溶菌酶的片段107 - 115为先导，通过将两个Ala残基（108和111）依次替换为不同的氨基酸进行两轮筛选，产生了对大肠杆菌ATCC 25922和金黄色葡萄球菌ATCC 29213分别具有4倍和20倍的抗微生物活性的新肽。这些结果加强了所提出的策略，该策略与简单易用的筛选工具相结合，将有助于市场所需的新治疗肽的快速开发。版权所有（C）2010欧洲肽协会和约翰威利父子有限公司。
The most challenging target in the design of new antimicrobial agents is the development of antibiotic resistance. Antimicrobial peptides are good candidates as lead compounds for the development of novel anti-infective drugs. Here we propose the sequential substitution of each Ala residue present in a lead peptide with known antimicrobial activity by specific amino acids, rationally chosen, that could enhance the activity of the resultant peptide. Taking the fragment 107-115 of the human lysozyme as lead, two-round screening by sequentially replacing both Ala residues (108 and 111) by distinct amino acids resulted in a novel peptide with 4- and 20-fold increased antimicrobial activity against Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 29213, respectively. These results reinforce the strategy proposed, which, in combination with simple and easy screening tools, will contribute to the rapid development of new therapeutic peptides required by the market. Copyright (C) 2010 European Peptide Society and John Wiley & Sons, Ltd.