期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 118, 期 6, 页码 1369-1374出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2006.08.016
关键词
HIV-1; gp120; CD4; EGCG; NMR; STD; flow cytometry
资金
- NCRR NIH HHS [RR0188] Funding Source: Medline
- NHLBI NIH HHS [HL079533, HL72705] Funding Source: Medline
- NIAID NIH HHS [AI41089, AI36211, AI27551] Funding Source: Medline
- NICHD NIH HHS [HD41983] Funding Source: Medline
- PHS HHS [RAT003084A] Funding Source: Medline
Background: The green tea flavonoid, epigallocatechin gallate (EGCG), has been proposed to have an anti-HIV-1 effect by preventing the binding of HIV-1 glycoprotein (gp) 120 to the CD4 molecule on T cells. Objective: To demonstrate that EGCG binds to the CD4 molecule at the gp120 attachment site and inhibits gp120 binding at physiologically relevant levels, thus establishing EGCG as a potential therapeutic treatment for HIV-1 infection. Methods: Nuclear magnetic resonance spectroscopy was used to examine the binding of EGCG and control, (-)-catechin, to CD4-IgG(2) (PRO 542 (R)). Gp120 binding to human CD4(+) T cells was analyzed by flow cytometry. Results: Addition of CD4 to EGCG produced a linear decrease in nuclear magnetic resonance signal intensity from EGCG but not from the control, (-)-catechin. In saturation transfer difference experiments, addition of 5.8 mu mol/L CD4 to 310 mu mol/L EGCG produced strong saturation at the aromatic rings of EGCG, but identical concentrations of (-)-catechin produced much smaller effects, implying EGCG/CD4 binding strong enough to reduce gp120/CD4 binding substantially. Molecular modeling studies suggested a binding site for EGCG in the D1 domain of CD4, the pocket that binds gp120. Physiologically relevant concentrations of EGCG (0.2 mu mol/L) inhibited binding of gp120 to isolated human CD4(+) T cells. Conclusion: We have demonstrated clear evidence of high-affinity binding of EGCG to the CD4 molecule with a K-d of approximately 10 nmol/L and inhibition of gp120 binding to human CD4(+) T cells. Clinical implications: Epigallocatechin gallate has potential use as adjunctive therapy in HIV-1 infection.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据