Department of Life Sciences , University of Modena and Reggio Emilia , Via Campi 103 , 41125 Modena , Italy.
Department of Biomedical Sciences, Metabolic and Neural Sciences , University of Modena and Reggio Emilia , Via Campi 287 , 41125 Modena , Italy.
J Med Chem. 2018 Aug 23;61(16):7374-7380. doi: 10.1021/acs.jmedchem.7b01699. Epub 2018 Aug 13.
LR and [d-Gln]LR peptides bind the monomer-monomer interface of human thymidylate synthase and inhibit cancer cell growth. Here, proline-mutated LR peptides were synthesized. Molecular dynamics calculations and circular dichroism spectra have provided a consistent picture of the conformational propensities of the [Pro ]-peptides. [Pro]LR and [Pro]LR show improved cell growth inhibition and similar intracellular protein modulation compared with LR. These represent a step forward to the identification of more rigid and metabolically stable peptides.
LR 和 [d-Gln]LR 肽结合人胸苷酸合成酶单体-单体界面并抑制癌细胞生长。本文合成了脯氨酸突变的 LR 肽。分子动力学计算和圆二色谱谱图为 [Pro]-肽的构象倾向提供了一致的图像。与 LR 相比，[Pro]LR 和 [Pro]LR 显示出更好的细胞生长抑制作用和相似的细胞内蛋白调节作用。这代表着向鉴定更刚性和代谢更稳定的肽迈出了一步。
