Ohki K, Kumagai K, Mitsuda S, Takano T, Kimura T, Ikuta K
Section of Serology, Institute of Immunological Science, Hokkaido University, Sapporo, Japan.
Vaccine. 1993;11(6):682-6. doi: 10.1016/0264-410x(93)90318-r.
We have previously identified CD4 peptides that exhibited blocking activity on human immunodeficiency virus type 1 (HIV-1) infection, i.e. CD4(68-130) and CD4(66-92) which include the region corresponding to the third complementarity-determining region of IgG. Here we describe a unique peptide derived from CD4(66-92), altered in amino acid sequence but not in composition, which was found to have increased anti-HIV-1 activity. The acidic amino acid residues in this scrambled peptide, S1, localized at the N-terminus, while in the native peptide they clustered at the C-terminus. On the other hand, a second scrambled peptide, S2, in which the acidic amino acid residues were fully dispersed, did not show any anti-HIV-1 activity. However, we could not identify any correlation between CD4(66-92) and S1 peptides by their hydrophobic or circular dichroism spectrum analyses. The results provide insight into the mechanisms of HIV-1 gp120 and CD4 interaction and may be useful as a new approach to AIDS therapy.
我们之前已经鉴定出对1型人类免疫缺陷病毒（HIV-1）感染具有阻断活性的CD4肽，即CD4(68-130)和CD4(66-92)，它们包含与IgG的第三个互补决定区相对应的区域。在此，我们描述了一种源自CD4(66-92)的独特肽，其氨基酸序列发生了改变，但组成未变，发现它具有增强的抗HIV-1活性。这种重排肽S1中的酸性氨基酸残基位于N端，而在天然肽中它们聚集在C端。另一方面，第二种重排肽S2中酸性氨基酸残基完全分散，未显示出任何抗HIV-1活性。然而，通过疏水或圆二色光谱分析，我们无法确定CD4(66-92)与S1肽之间的任何相关性。这些结果为深入了解HIV-1 gp120与CD4相互作用的机制提供了线索，并且可能作为艾滋病治疗的一种新方法。
