Identification of Novel Human Immunodeficiency Virus Type 1-Inhibitory Peptides Based on the Antimicrobial Peptide Database

Identification of Novel Human Immunodeficiency Virus Type 1-Inhibitory Peptides Based on the Antimicrobial Peptide Database
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DOI:
10.1128/aac.01448-09
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发表时间:
2010-03-01
影响因子:
4.9
通讯作者:
Buckheit, Robert W., Jr.
Buckheit, Robert W., Jr.
中科院分区:
医学2区
文献类型:
--
作者:
Wang, Guangshun;Watson, Karen M.;Buckheit, Robert W., Jr.

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为了根据抗菌肽数据库(APD;http://aps.unmc.edu/AP/main.php)鉴定新型抗HIV-1肽,我们筛选了30个候选肽,发现了11个肽,其50%有效浓度(EC50)<10μM,治疗指数(TI)高达17。此外,在通过金黄色素序列改组产生的8个肽(氨基酸组成相同但序列不同)中1.2 模拟,其中两个的 TI 是原始序列的两倍。由于数据库中的抗病毒肽的精氨酸/赖氨酸 (R/K) 比率 >1,因此两栖动物 maximin H5 和 dermaseptin S9 肽以及数据库衍生的 GLK-19 肽的 Arg 含量增加可改善 TI。这些例子表明,APD 是开发新型 HIV-1 抑制肽的丰富资源和有用工具。
To identify novel anti-HIV-1 peptides based on the antimicrobial peptide database (APD; http://aps.unmc.edu/AP/main.php), we have screened 30 candidates and found 11 peptides with 50% effective concentrations (EC50) of < 10 mu M and therapeutic indices (TI) of up to 17. Furthermore, among the eight peptides ( with identical amino acid compositions but different sequences) generated by shuffling the sequence of an aurein 1.2 analog, two had a TI twice that of the original sequence. Because antiviral peptides in the database have an arginine/lysine (R/K) ratio of >1, increases in the Arg contents of amphibian maximin H5 and dermaseptin S9 peptides and the database-derived GLK-19 peptide improved the TIs. These examples demonstrate that the APD is a rich resource and a useful tool for developing novel HIV-1-inhibitory peptides.