Soleimani Meysam, Mahnam Karim, Mirmohammad-Sadeghi Hamid, Sadeghi-Aliabadi Hojjat, Jahanian-Najafabadi Ali
Department of Pharmaceutical Biotechnology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
Biology Department, Faculty of Sciences, Shahrekord University, Shahrekord, I.R. Iran.
Res Pharm Sci. 2016 May-Jun;11(3):187-99.
p28 and NRC peptides are two anticancer peptides with various mechanisms have shown to be effective against breast cancer. Therefore, it seems that construction of a chimeric protein containing the two peptides might cause synergistic cytotoxic effects. However, since the two peptides bear opposite charges, production of a chimeric protein in which the two moieties do not intervene each other is difficult. In this study, our goal was to find a suitable peptide linker for the new chimeric protein in a manner that none of the peptides intervene the other's function. We selected some linkers with different characteristics and lengths and created a small library of the chimeric proteins harboring these linkers. Homology modeling and molecular dynamic simulation revealed that (PA)5P and (EAAAK)3 linkers can separate the p28 and NRC peptides effectively. Thus, the chimeric protein linked with (PA)5P or (EAAAK)3 linkers might show synergistic and stronger anticancer effects than the separate peptide moieties because they could exert their cytotoxic effects freely which is not influenced by the other part.
p28和NRC肽是两种具有多种作用机制的抗癌肽,已证明对乳腺癌有效。因此,构建一种包含这两种肽的嵌合蛋白可能会产生协同细胞毒性作用。然而,由于这两种肽带相反电荷,很难生产出一种两个部分互不干扰的嵌合蛋白。在本研究中,我们的目标是以一种肽不干扰另一种肽功能的方式,为新的嵌合蛋白找到合适的肽接头。我们选择了一些具有不同特性和长度的接头,并创建了一个包含这些接头的嵌合蛋白小文库。同源建模和分子动力学模拟表明,(PA)5P和(EAAAK)3接头可以有效分离p28和NRC肽。因此,与(PA)5P或(EAAAK)3接头连接的嵌合蛋白可能比单独的肽部分表现出协同且更强的抗癌作用,因为它们可以自由发挥其细胞毒性作用,而不受另一部分的影响。