Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity.
Synthetic CD4 peptide derivatives that inhibit HIV infection and cytopathicity.
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抑制 HIV 感染和细胞病变的合成 CD4 肽衍生物。
DOI：
10.1126/science.2969619
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Eiden,LE
中科院分区：
文献类型：
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作者：
Lifson,JD;Hwang,KM;Nara,PL;Fraser,B;Padgett,M;Dunlop,NM;Eiden,LE
测试了CD4分子的合成肽片段抑制人类免疫缺陷病毒(HIV)感染CD4+细胞和抑制HIV诱导的细胞融合的能力。一种由CD4(76-94)和合成副产物组成的多肽混合物，在标称浓度为125微摩尔时阻止了HIV诱导的细胞融合。在高效液相色谱中，该多肽混合物的抗合体活性不是在含有多肽CD4(76-94)本身的部分中发现的，而是在含有在自动合成中产生的衍生化多肽产物的侧面部分中发现的。使用在区域CD4(76-94)的衍生化缺失和替换多肽来证明序列特异性，这是苄基衍生化的要求，以及抗合体活性所需的核心七个残基片段。部分纯化的S-苄基-CD_4(83-94)肽混合物在标称浓度为≤32微摩尔时抑制艾滋病毒诱导的细胞融合。衍生的CD4多肽阻断了几个HIV分离株和SIV诱导的细胞融合，并阻断了四个外壳基因序列差异较大的HIV-1分离株在体外的感染。纯化的CD_4(83-94)在半胱氨酸86位和谷氨酸87位具有125微摩尔的抗合体活性。衍生化可以特异性地改变CD4全受体多肽片段的构象，增加它们的抗病毒效果。
Synthetic peptide segments of the CD4 molecule were tested for their ability to inhibit infection of CD4+cells by the human immunodeficiency virus (HIV) and to inhibit HIV-induced cell fusion. A peptide mixture composed of CD4(76-94), and synthesis side products, blocked HIV-induced cell fusion at a nominal concentration of 125 micromolar. Upon high-performance liquid chromatography, the antisyncytial activity of the peptide mixture was found not in the fraction containing the peptide CD4(76-94) itself, but in a side fraction containing derivatized peptide products generated in the automated synthesis. Derivatized deletion and substitution peptides in the region CD4(76-94) were used to demonstrate sequence specificity, a requirement for benzyl derivatization, and a core seven-residue fragment required for antisyncytial activity. A partially purifiedS-benzyl-CD4(83-94) peptide mixture inhibited HIV-induced cell fusion at a nominal concentration of ≤32 micromolar. Derivatized CD4 peptides blocked cell fusion induced by several HIV isolates and by the simian immunodeficiency virus, SIV, and blocked infection in vitro by four HIV-1 isolates with widely variant envelope gene sequences. Purified CD4(83-94) dibenzylated at cysteine 86 and glutamate 87 possessed antisyncytial activity at 125 micromolar. Derivatization may specifically alter the conformation of CD4 holoreceptor peptide fragments, increasing their antiviral efficacy.