Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission.
Maleic anhydride-modified chicken ovalbumin as an effective and inexpensive anti-HIV microbicide candidate for prevention of HIV sexual transmission.
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马来酸酐修饰的鸡卵清蛋白作为有效且廉价的抗 HIV 杀菌剂候选物，用于预防 HIV 性传播
DOI：
10.1186/1742-4690-7-37
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发表时间：
2010-04-26
期刊：
影响因子：
3.3
通讯作者：
Liu S
中科院分区：
文献类型：
--
作者：
Li L;Qiao P;Yang J;Lu L;Tan S;Lu H;Zhang X;Chen X;Wu S;Jiang S;Liu S
已有研究表明，3-羟基邻苯二酸酐（HP）修饰的牛乳蛋白β-乳球蛋白（β-LG）是一种很有前途的杀微生物剂。然而，人们对牛产品中朊病毒污染的潜在风险以及邻苯二甲酸酯衍生物的致癌潜力表示担忧。在这里，我们试图用一种非牛源性动物蛋白代替牛蛋白，并用另一种酸酐代替HP来开发抗HIV杀菌剂，以防止HIV的性传播。用马来酸酐（ML）、丁二酸酐（SU）和HP在不同条件和不同pH值下对蛋白质进行修饰。所有的无水修饰的球蛋白样蛋白都显示出强大的抗hiv活性，这与修饰蛋白中赖氨酸和精氨酸残基的百分比相关。我们选择马来酸酐修饰卵清蛋白（ML-OVA）进行进一步研究，因为OVA比β-LG更容易获得，ML比HP更安全。此外，ML-OVA对HIV-1、HIV-2、SHIV和SIV具有广泛的抗病毒活性。该修饰蛋白对人T细胞和阴道上皮细胞无或低的体外细胞毒性。它抵抗胰蛋白酶水解，可能是因为OVA中的赖氨酸和精氨酸残基被ML修饰。机制研究表明，ML-OVA通过靶向HIV-1病毒粒子上的gp120和宿主细胞上的CD4受体来抑制HIV-1的进入。ML-OVA是一种有效的HIV融合/进入抑制剂，有潜力成为一种有效、安全、廉价的抗HIV杀菌剂。
Previous studies have shown that 3-hydroxyphthalic anhydride (HP)-modified bovine milk protein, β-lactoglobulin (β-LG), is a promising microbicide candidate. However, concerns regarding the potential risk of prion contamination in bovine products and carcinogenic potential of phthalate derivatives were raised. Here we sought to replace bovine protein with an animal protein of non-bovine origin and substitute HP with another anhydride for the development of anti-HIV microbicide for preventing HIV sexual transmission. Maleic anhydride (ML), succinic anhydride (SU) and HP at different conditions and variable pH values were used for modification of proteins. All the anhydrate-modified globulin-like proteins showed potent anti-HIV activity, which is correlated with the percentage of modified lysine and arginine residues in the modified protein. We selected maleic anhydride-modified ovalbumin (ML-OVA) for further study because OVA is easier to obtain than β-LG, and ML is safer than HP. Furthermore, ML-OVA exhibited broad antiviral activities against HIV-1, HIV-2, SHIV and SIV. This modified protein has no or low in vitro cytotoxicity to human T cells and vaginal epithelial cells. It is resistant to trypsin hydrolysis, possibly because the lysine and arginine residues in OVA are modified by ML. Mechanism studies suggest that ML-OVA inhibits HIV-1 entry by targeting gp120 on HIV-1 virions and also the CD4 receptor on the host cells. ML-OVA is a potent HIV fusion/entry inhibitor with the potential to be developed as an effective, safe and inexpensive anti-HIV microbicide.
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影响因子：
5.4
作者：
Hsu, M;Harouse, JM;Cheng-Mayer, C
通讯作者：
Cheng-Mayer, C
影响因子：
5.4
作者：
Elton, D;Medcalf, L;Digard, P
通讯作者：
Digard, P
影响因子：
4.9
作者：
Dezzutti, CS;James, VN;Hart, CE
通讯作者：
Hart, CE
影响因子：
3.3
作者：
Lederman MM;Jump R;Pilch-Cooper HA;Root M;Sieg SF
通讯作者：
Sieg SF
影响因子：
5.4
作者：
Jiang, S;Lin, K;Lu, M
通讯作者：
Lu, M