Fülöp Lívia, Zarándi Márta, Datki Zsolt, Soós Katalin, Penke Botond
Department of Medical Chemistry, University of Szeged, Dóm tér 8, Szeged, Hungary.
Biochem Biophys Res Commun. 2004 Nov 5;324(1):64-9. doi: 10.1016/j.bbrc.2004.09.024.
Pr-IIGL(a), a derivative of the tetrapeptide beta-amyloid 31-34 (Abeta(31-34)), exerts controversial effects: it is toxic in a neuroblastoma culture, but it protects glial cells from the cytotoxic action of Abeta(1-42). For an understanding of this phenomenon, a new pentapeptide, RIIGL(a) was synthetized, and both compounds were studied by different physicochemical and biological methods. Transmission electron microscopic (TEM) studies revealed that Pr-IIGL(a) forms fibrillar aggregates, whereas RIIGL(a) does not form fibrils. Congo red binding studies furnished the same results. Aggregated Pr-IIGL(a) acts as a cytotoxic agent in neuroblastoma cultures, but RIIGL(a) does not display inherent toxicity. RIIGL(a) co-incubated with Abeta(1-42) inhibits the formation of mature amyloid fibres (TEM studies) and reduces the cytotoxic effect of fibrillar Abeta(1-42). These results indicate that RIIGL(a) is an effective inhibitor of both the aggregation and the toxic effects of Abeta(1-42) and can serve as a lead compound for the design of novel neuroprotective peptidomimetics.
Pr-IIGL(a)是四肽β-淀粉样蛋白31-34（Abeta(31-34)）的衍生物，其作用存在争议：它在神经母细胞瘤培养物中具有毒性，但能保护神经胶质细胞免受Abeta(1-42)的细胞毒性作用。为了解这一现象，合成了一种新的五肽RIIGL(a)，并通过不同的物理化学和生物学方法对这两种化合物进行了研究。透射电子显微镜（TEM）研究表明，Pr-IIGL(a)形成纤维状聚集体，而RIIGL(a)不形成纤维。刚果红结合研究也得出了相同的结果。聚集的Pr-IIGL(a)在神经母细胞瘤培养物中作为细胞毒性剂起作用，但RIIGL(a)不显示固有毒性。与Abeta(1-42)共同孵育的RIIGL(a)抑制成熟淀粉样纤维的形成（TEM研究），并降低纤维状Abeta(1-42)的细胞毒性作用。这些结果表明，RIIGL(a)是Abeta(1-42)聚集和毒性作用的有效抑制剂，可作为设计新型神经保护肽模拟物的先导化合物。
