Ohki K, Kimura T, Jones I M, Morita F, Ikuta K
Section of Serology, Hokkaido University, Sapporo, Japan.
Vaccine. 1994 Mar;12(4):343-50. doi: 10.1016/0264-410x(94)90099-x.
The interaction of the human immunodeficiency virus type 1 (HIV-1) envelope glycoprotein gp120 with CD4 CDR3-related peptide derivatives showing anti-HIV-1 activity has been studied. Conformational changes in gp120, which could affect its interaction with CD4 and its shedding from virions, were detected by fluorescence spectrum analysis of tryptophan residues after addition of peptide representative of the CD4 CDR3-related region, but not the CD4 CDR2-related region. Interestingly, the addition of scrambled peptide, S1 (with altered amino acid sequence compared with the native CDR3-related peptide but unaltered overall composition), which we recently showed to have stronger anti-HIV-1 activity than the original CDR3-related peptide, had no effects on the conformational change in gp120 or on its interaction with CD4 and its shedding from HIV-1 virions. However, all of the CDR3-related peptides, including S1, showed blocking effects on the binding of antibodies against gp120 V3 loop and C-terminus regions. Thus, we concluded that there were at least two separable activities of the CDR3-related peptides in anti-HIV-1 activity, i.e. induction of conformational changes in gp120, which could affect its binding to CD4 and to gp41 (as observed in native CDR3-related peptides), and inactivation of V3 loop and C-terminus regions in gp120 (as observed in all of the CDR3-related peptides, including S1).
对1型人类免疫缺陷病毒（HIV-1）包膜糖蛋白gp120与显示抗HIV-1活性的CD4 CDR3相关肽衍生物之间的相互作用进行了研究。通过添加代表CD4 CDR3相关区域而非CD4 CDR2相关区域的肽后，对色氨酸残基进行荧光光谱分析，检测到gp120中可能影响其与CD4相互作用及其从病毒粒子上脱落的构象变化。有趣的是，添加我们最近发现具有比原始CDR3相关肽更强抗HIV-1活性的乱序肽S1（与天然CDR3相关肽相比氨基酸序列改变但总体组成不变），对gp120的构象变化、其与CD4的相互作用以及其从HIV-1病毒粒子上的脱落均无影响。然而，所有的CDR3相关肽，包括S1，均对针对gp120 V3环和C末端区域的抗体结合显示出阻断作用。因此，我们得出结论，CDR3相关肽在抗HIV-1活性中至少有两种可分离的活性，即诱导gp120的构象变化，这可能影响其与CD4和gp41的结合（如在天然CDR3相关肽中观察到的），以及使gp120中的V3环和C末端区域失活（如在所有CDR3相关肽中观察到的，包括S1）。
