Giordano Cesare, Masi Annalisa, Pizzini Aldo, Sansone Anna, Consalvi Valerio, Chiaraluce Roberta, Lucente Gino
Istituto di Chimica Biomolecolare del CNR, Università La Sapienza, P.le A. Moro 5, 00185 Roma, Italy.
Eur J Med Chem. 2009 Jan;44(1):179-89. doi: 10.1016/j.ejmech.2008.03.036. Epub 2008 Apr 8.
Peptide derivatives 1-5, incorporating synthetic non-proteinogenic amino acids, related to the beta-amyloid 17-21 fragment of the amyloidogenic Abeta(1-40), and the N-protected decapeptide 6, corresponding to a dimeric sequence of the same fragment, have been synthesized. These compounds were designed by using Soto's pentapeptide Ac-LPFFD-NH(2) (iAbeta5p) as lead compound. Their activity as inhibitors of fibrillogenesis and stability against enzymatic degradation have been determined. Compounds 1, 5 and 6 are potent inhibitors in comparison to the lead compound. Exposure to chymotrypsin of peptide derivatives 1-5, all containing unnatural amino acids, shows increased stability as compared with iAbeta5p and 6. Conformational properties of the new compounds have been determined by CD and FT-IR spectroscopies.
已合成了肽衍生物1 - 5，其包含与淀粉样蛋白生成性Aβ(1 - 40)的β - 淀粉样蛋白17 - 21片段相关的合成非蛋白氨基酸，以及与相同片段的二聚体序列对应的N - 保护十肽6。这些化合物是以索托的五肽Ac - LPFFD - NH₂（iAbeta5p）作为先导化合物设计的。已测定了它们作为纤维形成抑制剂的活性以及对酶促降解的稳定性。与先导化合物相比，化合物1、5和6是有效的抑制剂。所有含有非天然氨基酸的肽衍生物1 - 5经胰凝乳蛋白酶处理后，与iAbeta5p和6相比显示出更高的稳定性。已通过圆二色光谱和傅里叶变换红外光谱测定了新化合物的构象性质。
