耶魯大學(xué)的研究人員開(kāi)發(fā)了一種分子,，該分子能夠加強(qiáng)機(jī)體對(duì)HIV和HIV感染的細(xì)胞的免疫應(yīng)答，此外還包括前列腺癌細(xì)胞,。這項(xiàng)研究結(jié)果發(fā)布在Journal of the American Chemical Society的在線版本上,，或能有助于開(kāi)發(fā)新的疾病療法,。
這種分子分別叫ARM-H（靶向定位HIV）,，和ARM-P（靶向定位前列腺癌細(xì)胞）,。在HIV感染的細(xì)胞中，該分子能夠同時(shí)綁定到已經(jīng)存在于血液中的抗體以及HIV蛋白上,。通過(guò)抗體包圍病原菌,，這個(gè)分子能夠?qū)Σ≡M(jìn)行標(biāo)記，激發(fā)機(jī)體自身的免疫系統(tǒng),。ARM-H通過(guò)綁定病毒外圍的蛋白,，同樣也可以保護(hù)健康的細(xì)胞，使其免受影響,。
研究人員不是通過(guò)直接殺死病原菌,，而是通過(guò)免疫系統(tǒng)。這類分子能夠調(diào)控我們的免疫系統(tǒng),，使其去做一些平時(shí)不會(huì)做的事情,。David Spiegel教授介紹說(shuō)。
由于HIV和癌癥能夠躲避機(jī)體的免疫系統(tǒng),，而且這兩種疾病的療法和疫苗都是比較難開(kāi)發(fā)的,。目前對(duì)于HIV和前列腺癌的療法，主要包括抗病毒藥,，輻射和化療,，但通常會(huì)伴隨嚴(yán)重的副作用。然而一些可行的抗體藥物又很難去大量生產(chǎn),，而且代價(jià)昂貴,，同樣的，其本身可能也有嚴(yán)重的副作用,。
研究小組發(fā)現(xiàn),，ARM-H和ARM-P分子的結(jié)構(gòu)簡(jiǎn)單，生產(chǎn)成本較低,，從理論上說(shuō)是能夠以藥片的形式生產(chǎn)的,。Spiegel介紹說(shuō)，由于它們不會(huì)靶向定位機(jī)體中一些重要的生物學(xué)過(guò)程,，所以副作用可能相對(duì)較小,。
這項(xiàng)研究將有助于開(kāi)發(fā)一種治療HIV和前列腺癌的全新方法，對(duì)人類健康來(lái)說(shuō)是非常重要的,。（生物谷Bioon.com）
生物谷推薦原始出處：
J. Am. Chem. Soc., 2009, 131 (45), pp 16392–16394 DOI: 10.1021/ja9057647
An Antibody-Recruiting Small Molecule That Targets HIV gp120
Christopher G. Parker?, Robert A. Domaoal?, Karen S. Anderson? and David A. Spiegel*??
Department of Chemistry, Yale University, 225 Prospect Street, P.O. Box 208107, New Haven, Connecticut 06520-8107, and Department of Pharmacology, Yale University School of Medicine, 333 Cedar Street, SHM B350B, New Haven, Connecticut 06520
HIV/AIDS is a global pandemic for which new treatment strategies are desperately needed. We have designed a novel small molecule, designated as ARM-H, that has the potential to interfere with HIV survival through two mechanisms: (1) by recruiting antibodies to gp120-expressing virus particles and infected human cells, thus enhancing their uptake and destruction by the human immune system, and (2) by binding the viral glycoprotein gp120, inhibiting its interaction with the human protein CD4 and preventing virus entry. Here we demonstrate that ARM-H is capable of simultaneously binding gp120, a component of the Env surface viral glycoprotein (found on the surface of both HIV and virus-infected cells) and anti-2,4-dinitrophenyl antibodies (already present in the human bloodstream). The ternary complex formed between the antibody, ARM-H, and gp120 is immunologically active and leads to the complement-mediated destruction of Env-expressing cells. Furthermore, ARM-H prevents virus entry into human T-cells and should therefore be capable of inhibiting virus replication through two mutually reinforcing mechanisms (inhibition of virus entry and antibody-mediated killing). These studies demonstrate the viable anti-HIV activity of antibody-recruiting small molecules and have the potential to initiate novel paradigms in HIV treatment.
