PNAS：用合成蛋白质阻断艾滋病病毒感染 对疱疹也有用！
美国研究人员在最新一期美国《国家科学院院刊》（PNAS）上报告说，他们在实验中利用一种合成蛋白质成功阻断了艾滋病病毒对健康细胞的入侵。这一成果将有助于研发出新的抗艾滋病药物。
美国威斯康星大学麦迪逊分校的一个研究小组介绍说，他们合成的这种蛋白质可以抑制艾滋病病毒的关键蛋白质gp41，使其不能与宿主细胞中的蛋白质发生交互作用，从而使病毒无法顺利入侵细胞。
研究人员解释说，gp41和宿主细胞内蛋白质的交互作用是艾滋病病毒感染并破坏人体细胞过程中的关键一环。过去科研人员曾研发各种药物，试图阻止这二者通过接触而产生相互作用，但都收效不大。一些药物中用来抑制gp41的合成蛋白质虽然部分有效，但体内的酶又会破坏其结构，使其不能发挥作用。
最新开发出的合成蛋白质由于在结构上作出了特殊改变，体内的酶根本就无法识别它。这种蛋白质有所“伪装”，同时又保存了原本的立体结构，从而可以顺利完成识别并抑制gp41的任务。
研究人员称，这一新成果不仅可以应用于对艾滋病的防治，也可应用于对流感病毒、埃博拉病毒等的防治，因为这些病毒都是通过蛋白质的交互作用而感染机体的。
PNAS August 17, 2009, doi: 10.1073/pnas.0902663106
Structural and biological mimicry of protein surface recognition by α/β-peptide foldamers
W. Seth Hornea, Lisa M. Johnsona, Thomas J. Ketasb, Per Johan Klasseb, Min Luc, John P. Mooreb and Samuel H. Gellmana,1
aDepartment of Chemistry, University of Wisconsin, 1101 University Avenue, Madison, WI 53706;
bDepartment of Microbiology and Immunology, Weill Medical College of Cornell University, New York, NY 10021; and
cDepartment of Biochemistry, Weill Medical College of Cornell University, New York, NY 10021
Unnatural oligomers that can mimic protein surfaces offer a potentially useful strategy for blocking biomedically important protein-protein interactions. Here we evaluate an approach based on combining α- and β-amino acid residues in the context of a polypeptide sequence from the HIV protein gp41, which represents an excellent testbed because of the wealth of available structural and biological information. We show that α/β-peptides can mimic structural and functional properties of a critical gp41 subunit. Physical studies in solution, crystallographic data, and results from cell-fusion and virus-infectivity assays collectively indicate that the gp41-mimetic α/β-peptides effectively block HIV-cell fusion via a mechanism comparable to that of gp41-derived α-peptides. An optimized α/β-peptide is far less susceptible to proteolytic degradation than is an analogous α-peptide. Our findings show how a two-stage design approach, in which sequence-based α→β replacements are followed by site-specific backbone rigidification, can lead to physical and biological mimicry of a natural biorecognition process.
