Theoretical design of a new chimeric protein for the treatment of breast cancer

• Published in: Research in pharmaceutical sciences Vol. 11; no. 3; pp. 187 - 199
• Main Authors: Soleimani, Meysam, Mahnam, Karim, Mirmohammad-Sadeghi, Hamid, Sadeghi-Aliabadi, Hojjat, Jahanian-Najafabadi, Ali
• Format: Journal Article
• Language: English
• Published: Iran Wolters Kluwer - Medknow Publications 01.05.2016; Medknow Publications and Media Pvt. Ltd; Medknow Publications & Media Pvt Ltd; Wolters Kluwer Medknow Publications
• Subjects: Breast cancer; Care and treatment; Fusion proteins; Genetic aspects; NRC; p28; Linker; Salt Bridge; Homology modeling; Molecular Dynamic Simulation; Original; Pharmacological research; Properties; Structure-activity relationships (Pharmacology); Molecular Dynamic Simulation; Linker; Salt Bridge; NRC; Homology modeling; p28
• ISSN: 1735-5362; 1735-9414

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.