Medicinal Chemistry and Drug Action, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
Arch Biochem Biophys. 2011 Sep 15;513(2):153-7. doi: 10.1016/j.abb.2011.07.008. Epub 2011 Jul 19.
Merozoite surface protein 2 (MSP2), one of the most abundant proteins on the surface of Plasmodium falciparum merozoites, is a promising malaria vaccine candidate. MSP2 is intrinsically unstructured and forms amyloid-like fibrils in solution. As this propensity of MSP2 to form fibrils in solution has the potential to impede its development as a vaccine candidate, finding an inhibitor that inhibits fibrillogenesis may enhance vaccine development. We have shown previously that EGCG inhibits the formation of MSP2 fibrils. Here we show that EGCG can alter the β-sheet-like structure of the fibril and disaggregate pre-formed fibrils of MSP2 into soluble oligomers. The fibril remodelling effects of EGCG and other flavonoids were characterised using Thioflavin T fluorescence assays, electron microscopy and other biophysical methods.
裂殖子表面蛋白 2（MSP2）是恶性疟原虫裂殖子表面最丰富的蛋白之一，是一种很有前途的疟疾疫苗候选物。MSP2 本质上无结构，在溶液中形成类似淀粉样的纤维。由于 MSP2 在溶液中形成纤维的这种倾向可能会阻碍其作为疫苗候选物的开发，因此寻找抑制纤维形成的抑制剂可能会促进疫苗的开发。我们之前已经表明，EGCG 可以抑制 MSP2 纤维的形成。在这里，我们表明 EGCG 可以改变纤维的β-折叠样结构，并将 MSP2 的预形成纤维解聚成可溶性寡聚物。使用硫黄素 T 荧光测定法、电子显微镜和其他生物物理方法来表征 EGCG 和其他类黄酮的纤维重塑作用。
