Tamamura H, Ishihara T, Otaka A, Murakami T, Ibuka T, Waki M, Matsumoto A, Yamamoto N, Fujii N
Faculty of Pharmaceutical Sciences, Kyoto University, Japan.
Biochim Biophys Acta. 1996 Nov 14;1298(1):37-44. doi: 10.1016/s0167-4838(96)00113-6.
We have previously found that T22 ([Tyr5, 12, Lys7]-polyphemusin II) exhibits strong anti-human immunodeficiency virus (HIV) activity comparable to that of 3'-azido-2', 3'-dideoxythymidine (AZT). The inhibition mechanism of T22 on HIV-replication has not been elucidated precisely yet, and hence the target molecules of T22 have not been identified. However, our recent research suggested that T22 exerts its effect by blocking virus-cell fusion at an early stage of HIV infection and that T22 might interact with an HIV envelope protein and/or a T-cell surface protein, both of which are critical for HIV infection. In this paper we demonstrated that T22 binds specifically to both gp120 (an envelope protein of HIV) and CD4 (a T-cell surface protein) and that both bindings can be inhibited by an anti-T22 antibody, using biosensor technology (BIAcoreTM) based on the principles of surface plasmon resonance. Linearization by the BIAcoreTM system (BIAlogue software) and nonlinear least squares analysis by curve fitting with exponential equations showed that both interactions have close dissociation constants (approximately 10(-7) M). The present study suggests that T22 inhibits the virus-cell fusion process through binding to both gp120 and CD4.
我们之前发现，T22（[酪氨酸5,12，赖氨酸7]-海胆精蛋白II）具有强大的抗人类免疫缺陷病毒（HIV）活性，与3'-叠氮-2'，3'-双脱氧胸苷（AZT）相当。T22对HIV复制的抑制机制尚未完全阐明，因此T22的靶分子也尚未确定。然而，我们最近的研究表明，T22通过在HIV感染早期阻断病毒-细胞融合发挥作用，并且T22可能与HIV包膜蛋白和/或T细胞表面蛋白相互作用，这两者对HIV感染都至关重要。在本文中，我们利用基于表面等离子体共振原理的生物传感器技术（BIAcoreTM）证明，T22能特异性结合gp120（HIV的一种包膜蛋白）和CD4（一种T细胞表面蛋白），并且这两种结合都能被抗T22抗体抑制。BIAcoreTM系统（BIAlogue软件）进行的线性化以及用指数方程进行曲线拟合的非线性最小二乘法分析表明，这两种相互作用都有相近的解离常数（约10^(-7) M）。本研究表明，T22通过与gp120和CD4结合来抑制病毒-细胞融合过程。
